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id="_NBK578061_"><span itemprop="name">Evidence review for step 1 treatment</span></h1><div class="subtitle">Hypertension in adults: diagnosis and management</div><p><b>Evidence review E</b></p><p><i>NICE Guideline, No. 136</i></p><p class="contrib-group"><h4>Authors</h4><span itemprop="author">National Guideline Centre (UK)</span>.</p><div class="half_rhythm">London: <a href="https://www.nice.org.uk" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=publisher"><span itemprop="publisher">National Institute for Health and Care Excellence (NICE)</span></a>; <span itemprop="datePublished">2019 Aug</span>.<div class="small">ISBN-13: <span itemprop="isbn">978-1-4731-3503-1</span></div></div><div><a href="/books/about/copyright/">Copyright</a> © NICE 2019.</div></div><div class="bkr_clear"></div></div><div id="ch5.s1"><h2 id="_ch5_s1_">1. Step 1 treatment</h2><div id="ch5.s1.1"><h3>1.1. Review question: Is monotherapy or combination antihypertensive therapy more clinically and cost effective for step 1 treatment for hypertension?</h3></div><div id="ch5.s1.2"><h3>1.2. Introduction</h3><p>Most individuals on treatment for hypertension are prescribed more than 1 medication to achieve their target blood pressure. One of the reasons for this is that different medications act on different pathways of blood pressure regulation. When 1 pathway is modified by a medication, the other pathways may compensate to keep the blood pressure elevated. It may therefore be more clinically and cost-effective to start more than 1 antihypertensive medication at the same time, thus potentially achieving the target blood pressure quicker and with fewer visits to the healthcare provider. In this chapter, the evidence for this approach is compared to that for starting with monotherapy.</p></div><div id="ch5.s1.3"><h3>1.3. PICO table</h3><p>For full details, see the review protocol in <a href="#ch5.appa">appendix A</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch5tab1"><a href="/books/NBK578061/table/ch5.tab1/?report=objectonly" target="object" title="Table 1" class="img_link icnblk_img figpopup" rid-figpopup="figch5tab1" rid-ob="figobch5tab1"><img class="small-thumb" src="/books/NBK578061/table/ch5.tab1/?report=thumb" src-large="/books/NBK578061/table/ch5.tab1/?report=previmg" alt="Table 1. PICO characteristics of review question." /></a><div class="icnblk_cntnt"><h4 id="ch5.tab1"><a href="/books/NBK578061/table/ch5.tab1/?report=objectonly" target="object" rid-ob="figobch5tab1">Table 1</a></h4><p class="float-caption no_bottom_margin">PICO characteristics of review question. </p></div></div></div><div id="ch5.s1.4"><h3>1.4. Methods and process</h3><p>This evidence review was developed using the methods and process described in Developing NICE guidelines: the manual.<a class="bibr" href="#ch5.ref155" rid="ch5.ref155"><sup>155</sup></a> Methods specific to this review question are described in the review protocol in <a href="#ch5.appa">appendix A</a>.</p><p>Declarations of interest were recorded according to NICE’s 2014 conflicts of interest policy.</p></div><div id="ch5.s1.5"><h3>1.5. Clinical evidence</h3><div id="ch5.s1.5.1"><h4>1.5.1. Included studies</h4><p>Three studies were included in the review<a class="bibr" href="#ch5.ref13" rid="ch5.ref13"><sup>13</sup></a><sup>,</sup>
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<a class="bibr" href="#ch5.ref14" rid="ch5.ref14"><sup>14</sup></a><sup>,</sup>
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<a class="bibr" href="#ch5.ref47" rid="ch5.ref47"><sup>47</sup></a><sup>,</sup>
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<a class="bibr" href="#ch5.ref52" rid="ch5.ref52"><sup>52</sup></a><sup>,</sup>
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<a class="bibr" href="#ch5.ref133" rid="ch5.ref133"><sup>133</sup></a><sup>,</sup>
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<a class="bibr" href="#ch5.ref139" rid="ch5.ref139"><sup>139</sup></a><sup>,</sup>
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<a class="bibr" href="#ch5.ref148" rid="ch5.ref148"><sup>148</sup></a>; these are summarised in <a class="figpopup" href="/books/NBK578061/table/ch5.tab2/?report=objectonly" target="object" rid-figpopup="figch5tab2" rid-ob="figobch5tab2">Table 2</a> below. Evidence from these studies is summarised in the clinical evidence summary below (<a class="figpopup" href="/books/NBK578061/table/ch5.tab3/?report=objectonly" target="object" rid-figpopup="figch5tab3" rid-ob="figobch5tab3">Table 3</a>).</p><p>See also the study selection flow chart in <a href="#ch5.appc">appendix C</a>, study evidence tables in <a href="#ch5.appd">appendix D</a>, forest plots in <a href="#ch5.appe">appendix E</a> and GRADE tables in <a href="#ch5.appf">appendix F</a>.</p></div><div id="ch5.s1.5.2"><h4>1.5.2. Excluded studies</h4><p>Cochrane reviews relevant to this review question were identified. Li 2014<a class="bibr" href="#ch5.ref132" rid="ch5.ref132"><sup>132</sup></a> was excluded due to an incorrect population. Garjon 2017<a class="bibr" href="#ch5.ref89" rid="ch5.ref89"><sup>89</sup></a> was excluded due to no relevant outcomes.</p><p>See the excluded studies list in <a href="#ch5.appi">appendix I</a>.</p></div><div id="ch5.s1.5.3"><h4>1.5.3. Summary of clinical studies included in the evidence review</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch5tab2"><a href="/books/NBK578061/table/ch5.tab2/?report=objectonly" target="object" title="Table 2" class="img_link icnblk_img figpopup" rid-figpopup="figch5tab2" rid-ob="figobch5tab2"><img class="small-thumb" src="/books/NBK578061/table/ch5.tab2/?report=thumb" src-large="/books/NBK578061/table/ch5.tab2/?report=previmg" alt="Table 2. Summary of studies included in the evidence review." /></a><div class="icnblk_cntnt"><h4 id="ch5.tab2"><a href="/books/NBK578061/table/ch5.tab2/?report=objectonly" target="object" rid-ob="figobch5tab2">Table 2</a></h4><p class="float-caption no_bottom_margin">Summary of studies included in the evidence review. </p></div></div><p>See <a href="#ch5.appd">appendix D</a> for full evidence tables.</p></div><div id="ch5.s1.5.4"><h4>1.5.4. Quality assessment of clinical studies included in the evidence review</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch5tab3"><a href="/books/NBK578061/table/ch5.tab3/?report=objectonly" target="object" title="Table 3" class="img_link icnblk_img figpopup" rid-figpopup="figch5tab3" rid-ob="figobch5tab3"><img class="small-thumb" src="/books/NBK578061/table/ch5.tab3/?report=thumb" src-large="/books/NBK578061/table/ch5.tab3/?report=previmg" alt="Table 3. Clinical evidence summary: monotherapy versus combination (adults with hypertension and type 2 diabetes strata)." /></a><div class="icnblk_cntnt"><h4 id="ch5.tab3"><a href="/books/NBK578061/table/ch5.tab3/?report=objectonly" target="object" rid-ob="figobch5tab3">Table 3</a></h4><p class="float-caption no_bottom_margin">Clinical evidence summary: monotherapy versus combination (adults with hypertension and type 2 diabetes strata). </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch5tab4"><a href="/books/NBK578061/table/ch5.tab4/?report=objectonly" target="object" title="Table 4" class="img_link icnblk_img figpopup" rid-figpopup="figch5tab4" rid-ob="figobch5tab4"><img class="small-thumb" src="/books/NBK578061/table/ch5.tab4/?report=thumb" src-large="/books/NBK578061/table/ch5.tab4/?report=previmg" alt="Table 4. Clinical evidence summary: monotherapy versus combination (adults with hypertension and without type 2 diabetes strata)." /></a><div class="icnblk_cntnt"><h4 id="ch5.tab4"><a href="/books/NBK578061/table/ch5.tab4/?report=objectonly" target="object" rid-ob="figobch5tab4">Table 4</a></h4><p class="float-caption no_bottom_margin">Clinical evidence summary: monotherapy versus combination (adults with hypertension and without type 2 diabetes strata). </p></div></div><p>See <a href="#ch5.appf">appendix F</a> for full GRADE tables.</p></div></div><div id="ch5.s1.6"><h3>1.6. Economic evidence</h3><div id="ch5.s1.6.1"><h4>1.6.1. Included studies</h4><p>No relevant health economic studies were identified.</p></div><div id="ch5.s1.6.2"><h4>1.6.2. Excluded studies</h4><p>Five economic studies relating to this review question were identified but were excluded due to limited applicability or methodological limitations.<a class="bibr" href="#ch5.ref119" rid="ch5.ref119"><sup>119</sup></a><sup>,</sup><a class="bibr" href="#ch5.ref146" rid="ch5.ref146"><sup>146</sup></a><sup>,</sup><a class="bibr" href="#ch5.ref215" rid="ch5.ref215"><sup>215</sup></a><sup>,</sup><a class="bibr" href="#ch5.ref192" rid="ch5.ref192"><sup>192</sup></a><sup>,</sup><a class="bibr" href="#ch5.ref204" rid="ch5.ref204"><sup>204</sup></a> This includes 1 study included in the previous guideline that was not applicable because it compared treatment to no treatment as opposed to combination therapy versus monotherapy.</p><p>These are listed in <a href="#ch5.appi">appendix I</a> with the reasons for exclusion given.</p><p>See also the health economic study selection flow chart in <a href="#ch5.appg">appendix G</a>.</p></div><div id="ch5.s1.6.3"><h4>1.6.3. Resource costs</h4><p>Some illustrative costs are demonstrated below of monotherapies and combination therapies, based on the drugs that were used in the clinical evidence identified.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch5tab5"><a href="/books/NBK578061/table/ch5.tab5/?report=objectonly" target="object" title="Table 5" class="img_link icnblk_img figpopup" rid-figpopup="figch5tab5" rid-ob="figobch5tab5"><img class="small-thumb" src="/books/NBK578061/table/ch5.tab5/?report=thumb" src-large="/books/NBK578061/table/ch5.tab5/?report=previmg" alt="Table 5. UK costs of anti-hypertensives (monotherapies or combinations)." /></a><div class="icnblk_cntnt"><h4 id="ch5.tab5"><a href="/books/NBK578061/table/ch5.tab5/?report=objectonly" target="object" rid-ob="figobch5tab5">Table 5</a></h4><p class="float-caption no_bottom_margin">UK costs of anti-hypertensives (monotherapies or combinations). </p></div></div><p>Also illustrated below are costs of cardiovascular events to demonstrate costs that might be avoided from avoiding events. It is important to note that these are from NHS reference costs and are therefore the costs related to initial hospitalisation ONLY.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch5tab6"><a href="/books/NBK578061/table/ch5.tab6/?report=objectonly" target="object" title="Table 6" class="img_link icnblk_img figpopup" rid-figpopup="figch5tab6" rid-ob="figobch5tab6"><img class="small-thumb" src="/books/NBK578061/table/ch5.tab6/?report=thumb" src-large="/books/NBK578061/table/ch5.tab6/?report=previmg" alt="Table 6. Costs of hospitalisation from cardiovascular events." /></a><div class="icnblk_cntnt"><h4 id="ch5.tab6"><a href="/books/NBK578061/table/ch5.tab6/?report=objectonly" target="object" rid-ob="figobch5tab6">Table 6</a></h4><p class="float-caption no_bottom_margin">Costs of hospitalisation from cardiovascular events. </p></div></div><div id="ch5.s1.6.3.1"><h5>Example costings</h5><p>Assumptions:
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<ul id="ch5.l8"><li id="ch5.lt38" class="half_rhythm"><div>The medications are those used in the trials in the clinical review: monotherapy is Enalapril 10 mg per day, and dual therapy is perindopril erbumine plus indapamide in separate pills of dose 2 mg and 1.5 mg per day respectively.</div></li></ul></p><p>This may not necessarily be the most common drugs that would be used in UK practice.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch5tab7"><a href="/books/NBK578061/table/ch5.tab7/?report=objectonly" target="object" title="Table 7" class="img_link icnblk_img figpopup" rid-figpopup="figch5tab7" rid-ob="figobch5tab7"><img class="small-thumb" src="/books/NBK578061/table/ch5.tab7/?report=thumb" src-large="/books/NBK578061/table/ch5.tab7/?report=previmg" alt="Table 7. Cost trade-off illustration." /></a><div class="icnblk_cntnt"><h4 id="ch5.tab7"><a href="/books/NBK578061/table/ch5.tab7/?report=objectonly" target="object" rid-ob="figobch5tab7">Table 7</a></h4><p class="float-caption no_bottom_margin">Cost trade-off illustration. </p></div></div></div></div></div><div id="ch5.s1.7"><h3>1.7. Evidence statements</h3><div id="ch5.s1.7.1"><h4>1.7.1. Clinical evidence statements</h4><div id="ch5.s1.7.1.1"><h5>Monotherapy versus combination (adults with hypertension and type 2 diabetes strata)</h5><p>Very low quality evidence from 1 study with 481 participants showed a clinically important benefit of combination therapy compared to monotherapy for serious cardiovascular events in people with type 2 diabetes.</p><p>Very low to low quality evidence from 1 study with 481 participants showed no clinically important difference for change in creatinine clearance, discontinuation due to adverse events and dizziness. Very low quality evidence from 1 study with 538 participants showed no clinically important difference for discontinuation due to adverse events.</p></div><div id="ch5.s1.7.1.2"><h5>Monotherapy versus combination (adults with hypertension and without type 2 diabetes strata)</h5><p>High quality evidence from 1 study with a total of 457 participants showed no clinically important difference between monotherapy or combination therapy for change in creatinine. Very low quality evidence from 1 study with 418 participants showed no clinically important difference for discontinuation due to adverse events.</p></div></div><div id="ch5.s1.7.2"><h4>1.7.2. Health economic evidence statements</h4><p>No relevant economic evaluations were identified.</p></div></div><div id="ch5.s1.8"><h3>1.8. The committee’s discussion of the evidence</h3><div id="ch5.s1.8.1"><h4>1.8.1. Interpreting the evidence</h4><div id="ch5.s1.8.1.1"><h5>1.8.1.1. The outcomes that matter most</h5><p>The committee considered all-cause mortality, quality of life, stroke and myocardial infarction (MI) to be critical outcomes for decision-making. Heart failure, angina, vascular procedures, and discontinuation due to adverse events as well as specific adverse events and resource use were considered important outcomes for decision-making. In the population without type 2 diabetes, evidence was identified for adverse events only (discontinuation due to adverse events, change in creatinine levels). In people with type 2 diabetes, the only evidence identified was an indirect outcome of major cardiovascular events and adverse event outcomes (change in creatinine clearance, dizziness and discontinuation due to adverse events).</p></div><div id="ch5.s1.8.1.2"><h5>1.8.1.2. The quality of the evidence</h5><p>The committee discussed that the evidence was limited; from 3 studies, only 1 of which reported a critical outcome (serious cardiovascular events), albeit an indirect composite measure of the individual outcomes the committee were interested in. All of the evidence for people with hypertension and type 2 diabetes was low or very low quality due mainly to risk of bias, indirectness and imprecision. Risk of bias was rated as high because of high attrition rates due to participants dropping out of trials or being lost to follow up. The evidence was also downgraded due to population indirectness. Some participants included within the evidence were outside of the scope of this review question, such as those with moderate to severe chronic kidney disease (CKD). The population included within the evidence was based on studies with small sample sizes.</p><p>The only high quality evidence available was for change in creatinine for adults with hypertension and without type 2 diabetes. However, this was also only from a single, relatively small study.</p></div><div id="ch5.s1.8.1.3"><h5>1.8.1.3. Benefits and harms</h5><p>The committee discussed that there was an indication that initiating dual therapy may be better than monotherapy as the step 1 treatment option, in terms of reducing cardiovascular events in a diabetes population, albeit from very low quality evidence. The evidence for people without type 2 diabetes was more limited, with evidence available for the outcomes of change in creatinine and discontinuation due to adverse events, neither of which were cardiovascular events so determining the benefit of treatment was not possible.</p><p>It was noted that there was conflicting evidence from 2 separate studies in terms of discontinuation due to adverse events; however, the committee agreed it was more intuitive to see more discontinuation in people with dual therapy. Although this was also low quality evidence and a relatively small numbers of events, the committee considered that this did not demonstrate any substantial increase in harm from dual therapy.</p><p>In considering the body of evidence, the committee discussed that it was disappointing that there was not more evidence on patient important outcomes available to demonstrate a benefit of dual therapy as a step 1 treatment option. The committee was aware of epidemiological and observational evidence suggesting that many people do start on 2 drugs and have good outcomes as a result such as quicker reductions in blood pressure, which result in mortality benefit; furthermore, observational evidence suggests that not optimising management for people with hypertension early can have a substantial impact on subsequent quality of life. However, the committee agreed that the level of available evidence identified in this review was insufficient to change the recommendations from CG127.</p><p>The committee discussed the evidence identified in 2011 in CG127<a class="bibr" href="#ch5.ref154" rid="ch5.ref154"><sup>154</sup></a> related to step 1 treatment. The recommendations were stratified by age and family origin reflecting data from clinical trials showing differential effects of the different classes of blood pressure lowering drugs on blood pressure lowering and clinical outcomes in younger (less than 55 years old) versus older people and in black people of African or Caribbean descent. Three studies and an age-stratified analysis from a fourth study also compared blood pressure response across various drug classes and identified ACE inhibitors and beta-blockers as more effective at lowering blood pressure in younger people, when compared to calcium channel-blockers or thiazide-type diuretics. The evidence for ACE inhibitor and ARBs were closely correlated (although lacked head-to-head evidence) and the previous guideline recommended that these treatments should be treated as equal in terms of efficacy; however, due to cost differences, it was considered that ACE inhibitors should be initiated first and an ARB considered an alternative for when an ACE inhibitor was poorly tolerated. The 2011 guideline did not identify evidence to show any consistent trend favouring 1 drug class over the other. The committee agreed it was appropriate to retain these recommendations but to keep in mind that ACE inhibitors and ARBs are now equal in terms of both cost and efficacy.</p><p>The committee also discussed step 1 treatment in people with type 2 diabetes, and noted that NG28 recommended ACE inhibitors as step 1 treatment rather than ARBs. The committee noted that this was based both on differences in costs and on limited evidence of a difference in reno-protective benefits between the two treatments. The committee agreed that from their current clinical experience ARBs and ACE inhibitors were similarly effective are were not aware of evidence to contradict this.</p><p>However, the committee agreed that beta-blockers are not often used as antihypertensive treatment in current practice and recent meta-analysis (not relevant to this review protocol) have demonstrated this class to be low efficacy for the treatment of hypertension in terms of improving cardiovascular outcomes. The committee discussed whether these drugs are ever an appropriate choice for people with hypertension. They discussed people with evidence of a high sympathetic drive and noted that the primary cause should be addressed rather than treating the hypertension primarily and that in these cases, beta-blockers would not be the most appropriate choice of drug. The committee therefore agreed not to retain the recommendations related to the use of beta-blockers in people under 55 years.</p><p>For people of black African or African Caribbean family origin with type 2 diabetes, the previous recommendation from the type 2 diabetes guideline (NG28) was to offer an ACE inhibitor and either a diuretic or a calcium-channel blocker as step 1 dual therapy. The committee discussed what had informed those recommendations. There were no trials looking at combination treatments in this group and so results from monotherapy studies were considered. There was evidence that CCBs provided better cardiovascular outcomes in black individuals with hypertension compared to ACEi, and that A drugs resulted in improved outcomes in all individuals with diabetes. Additionally, physiological studies suggested lower efficacy of A drugs in black and/or older individuals. Based on these observations it was decided by consensus that for black, hypertensive, diabetic individuals the first-line combination of A+C/D should be used. Although there was some evidence identified for this question on people with hypertension and diabetes, it was only from a single small study, and the committee did not consider this strong enough to base a recommendation on. People with hypertension but no diabetes are offered a CCB in the hypertension guideline, but an ACE inhibitor or ARB is more suitable for those with diabetes as mentioned above. It was discussed how in practice the step 1 dual therapy recommendation for people of black African or African Caribbean family origin is not generally current practice. Black people often show inadequate response to ACE inhibitors and therefore require additional drugs. What tends to happen is an ACE inhibitor is given for step 1 instead of the more appropriate ARB and hence treatment may be escalated more quickly to dual therapy for this group. In summary, the recommendation for step 1 dual therapy was not retained for this group in NG28. The committee noted that considerations may apply in the presence of target organ damage such as microalbuminuria as these patients are at higher CVD risk. The recommendation to offer an ARB in preference for an ACE inhibitor for people of black African or African Caribbean family origin either with or without type 2 diabetes was also retained. The previous guideline committee (CG127) considered that people of black African or Caribean family origin that take ACE inhibitors have an increased risk of developing angioedema which can be life threatening. Although the incidence of this adverse event is low, the previous committee suggested that an ARB in preference to an ACE inhibitor should be considered for such patients.</p></div></div><div id="ch5.s1.8.2"><h4>1.8.2. Cost effectiveness and resource use</h4><p>Five studies were identified that may be relevant for this question but were selectively excluded due to methodological limitations. One of these was a study included in the previous guideline comparing treatment versus no treatment based on resource use from the HYVET study in an elderly population. A no treatment comparison is not of interest in this question but that study fell under the question of step 1 treatment in people aged over 80 in the previous guideline and has therefore been selectively excluded because the comparison is not relevant to this update of the review.</p><p>The committee was presented with some examples of unit costs of monotherapy and dual therapy based on the drugs used in the clinical studies, as well as some illustrative hospitalisation costs for cardiovascular events.</p><p>Dual therapy treatments are likely to have higher costs. In theory, 2 medications instead of 1 may also lead to more adverse events, which also needs to be traded off against benefit. This was not clear from the clinical review, which found no difference in discontinuation rates. The major impact on effectiveness that would be traded-off against the additional drug use is the impact on cardiovascular events or mortality. The clinical review showed that there were 39 fewer serious cardiovascular events with the dual therapy treatment than with the monotherapy, in a population with hypertension and type 2 diabetes. Cardiovascular events are likely to be events like myocardial infarction or stroke, which are very costly to treat and can have a long-term impact on quality of life. Therefore, any events avoided could be argued as being significant. This evidence was of very low quality, however, and was from only 1 study and therefore may not be sufficient evidence to change practice, as the committee cannot be confident that these outcomes are likely to represent the true outcomes in the general population with such little evidence.</p><p>As an example of some costing illustrations, a cohort of 1000 people taking monotherapy or dual therapy for 12 months would lead to higher intervention costs for the dual therapy arm (£19,945 versus £63,997 respectively) (based on the drugs that were used in the included trial). Trading this off against the cardiovascular event outcomes from the clinical review, shows that monotherapy is overall more expensive than dual therapy. This is a very simplified example, and there are a number of factors that haven’t been captured. Cardiovascular event costs are likely to be higher than just initial hospitalisation costs such as including follow-ups and rehabilitation perhaps. There is no quality of life captured, but events would have a detriment to quality of life. These factors are likely to favour dual therapy. However, different drugs also have different costs, and dual therapy in a single pill may be more expensive because of the ease of having to take only 1 pill but have the benefit of 2 drugs. There are no adverse events included or other costs associated with treatment like monitoring, which might be higher in a dual therapy strategy. Therefore, even if dual therapy was overall a more expensive strategy, it is uncertain if this would be cost effective.</p><p>It is also uncertain in what timeframe people might be reviewed, in which case some people on monotherapy would go on to other lines of treatment anyway. This argument is implying that if people do not stay on monotherapy for very long (with uncontrolled hypertension), then the difference in intervention will only apply for a short duration. Effectively, what is being compared is bringing forward step 2 treatment versus starting on step 1 treatment. Some data from UK GP practices on the proportion of hypertensives on different numbers of drugs showed (depending on age and sex) that around 40–60% of people are on 1 drug, 30–40% of people are on 2 drugs, and 10–20% are on 3 drugs. Therefore, most people tend to stay on 1 drug, implying it would be a big change to start on 2 drugs. However, it is unclear if their hypertension is controlled or uncontrolled on 1 drug. Those who remain controlled on 1 drug would have lower medication costs for the same outcome although 2 drugs are known to get a person to a target more quickly. If monitoring following initiation of monotherapy occurred in a timely way, then those uncontrolled on 1 drug would be stepped up to step 2 drugs more quickly. However, being on step 2 treatment from the beginning may avoid some events that would have happened in that space of time. In summary, there are many factors to consider that make it uncertain if starting on dual therapy is cost effective.</p><p>The committee were not able to make a recommendation about starting on dual therapy (whether that is 2 drugs in 1 pill or separately) because of the limited clinical evidence, and there was no robust cost effectiveness evidence. The committee discussed the potential for treatment inertia and the factors related to that such as people being asymptomatic and the discussion that happens about benefits and risks of taking, changing or adding treatments. The frequency of monitoring to assess the effectiveness of treatment can also be variable. As the committee couldn’t make a recommendation favouring starting with dual therapy, a research recommendation was made to identify in which groups dual therapy should be initiated.</p><p>Some of the recommendations from the previous hypertension guideline were edited, including removing a recommendation on when to use beta-blockers, as these are not used very much in practice, and removing references to low cost ARBs, as ACE inhibitors and ARBs are similarly low cost now. In general, the previous recommendations were agreed to still be appropriate and represent good practice. These were based on a combination of clinical evidence and cost effectiveness evidence, as a model in the 2004 guideline comparing monotherapies for step 1 treatment (for which costs were updated in the 2011 guideline) showed that CCBs were generally the most cost effective. In higher risk people, thiazides were shown to be the most cost effective for people at high risk of heart failure. A sensitivity analysis on age showed that ACE inhibitors or ARBs were likely to be the most cost effective.</p><p>The committee’s view was that a monotherapy of an ACE inhibitor could be offered to anyone with diabetes of any age or family origin, as the dual therapy recommendation for the black people of African or African Caribbean family origin population is not generally followed in practice and was not based on evidence. Given that current practice generally already offers an ACE inhibitor to people with diabetes regardless of age or family origin with an ARB as an alternative, this is unlikely to have a large impact on practice.</p></div><div id="ch5.s1.8.3"><h4>1.8.3. Other factors the committee took into account</h4><p>The committee reviewed the wording of the recommendations in the previous 2011 hypertension guideline (CG127) and highlighted that if a thiazide like diuretic was being offered, indapamide is likely to be the drug that is used. The previous wording of the recommendation may have implied chlortalidone should be first choice, by the nature of it being listed first; however, chlortalidone hasn’t become more widely available to European market as was hoped, and therefore this has been removed from the recommendation.</p><p>The committee further noted that there were safety concerns regarding the use of ACE inhibitors and ARBs in pregnant women. A footnote was added to this recommendation to alert to MHRA safety updates.</p><p>It was noted that it was important to highlight that medicines should be taken as prescribed in order to be most effective, and so a recommendation was made to highlight that this should be discussed with the person and that adherence should be supported.</p></div></div></div><div id="ch5.rl.r1"><h2 id="_ch5_rl_r1_">References</h2><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><div class="bk_ref" id="ch5.ref1">Aalbers
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J. Reduced blood pressure variability in ASCOT-BPLA trial favours use of amlodipine/perindopril combination to reduce stroke risk. Cardiovascular Journal of Africa. 2010; 21(2):115 [<a href="/pmc/articles/PMC5566084/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5566084</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20532438" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20532438</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><div class="bk_ref" id="ch5.ref2">Abate
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G, Zito
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M, Carbonin
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PU, Cocchi
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A, Cucinotta
|
|
D, Manopulo
|
|
R
|
|
et al. Pinacidil and hydrochlorothiazide alone or in combination in the treatment of hypertension in the elderly. Current Therapeutic Research, Clinical and Experimental. 1998; 59(1):62–71</div></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><div class="bk_ref" id="ch5.ref3">Amir
|
|
M, Cristal
|
|
N, Bar-On
|
|
D, Loidl
|
|
A. Does the combination of ACE inhibitor and calcium antagonist control hypertension and improve quality of life? The LOMIR-MCT-IL study experience. Blood Pressure Supplement. 1994; 1:40–2 [<a href="https://pubmed.ncbi.nlm.nih.gov/8205297" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8205297</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><div class="bk_ref" id="ch5.ref4">Anan
|
|
F, Takahashi
|
|
N, Ooie
|
|
T, Yufu
|
|
K, Hara
|
|
M, Nakagawa
|
|
M
|
|
et al. Effects of valsartan and perindopril combination therapy on left ventricular hypertrophy and aortic arterial stiffness in patients with essential hypertension. European Journal of Clinical Pharmacology. 2005; 61(5–6):353–9 [<a href="https://pubmed.ncbi.nlm.nih.gov/15918057" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15918057</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><div class="bk_ref" id="ch5.ref5">Andersson
|
|
OK. Improved efficacy with maintained tolerability in the treatment of primary hypertension. Comparison between the felodipine-metoprolol combination tablet and monotherapy with enalapril. Swedish Multicentre Group. Journal of Human Hypertension. 1999; 13(1):55–60 [<a href="https://pubmed.ncbi.nlm.nih.gov/9928753" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9928753</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>6.</dt><dd><div class="bk_ref" id="ch5.ref6">Anderton
|
|
JL, Vallance
|
|
BD, Stanley
|
|
NN, Crowe
|
|
PF, Mittra
|
|
B, Perks
|
|
WH. Atenolol and sustained release nifedipine alone and in combination in hypertension. A randomised, double-blind, crossover study. Drugs. 1988; 35:(Suppl 4):22–6 [<a href="https://pubmed.ncbi.nlm.nih.gov/3288467" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3288467</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>7.</dt><dd><div class="bk_ref" id="ch5.ref7">Andreadis
|
|
EA, Sfakianakis
|
|
ME, Tsourous
|
|
GI, Georgiopoulos
|
|
DX, Fragouli
|
|
EG, Katsanou
|
|
PM
|
|
et al. Differential impact of angiotensin receptor blockers and calcium channel blockers on arterial stiffness. International Angiology. 2010; 29(3):266–72 [<a href="https://pubmed.ncbi.nlm.nih.gov/20502415" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20502415</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>8.</dt><dd><div class="bk_ref" id="ch5.ref8">Andreadis
|
|
EA, Tsourous
|
|
GI, Marakomichelakis
|
|
GE, Katsanou
|
|
PM, Fotia
|
|
ME, Vassilopoulos
|
|
CV
|
|
et al. High-dose monotherapy vs low-dose combination therapy of calcium channel blockers and angiotensin receptor blockers in mild to moderate hypertension. Journal of Human Hypertension. 2005; 19(6):491–6 [<a href="https://pubmed.ncbi.nlm.nih.gov/15759025" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15759025</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>9.</dt><dd><div class="bk_ref" id="ch5.ref9">Anonymous. Low-dose captopril for the treatment of mild to moderate hypertension. Hypertension. 1983; 5(5 Suppl 3):III139–44 [<a href="https://pubmed.ncbi.nlm.nih.gov/6354929" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6354929</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>10.</dt><dd><div class="bk_ref" id="ch5.ref10">Anonymous. Nifedipine and atenolol singly and combined for treatment of essential hypertension: Comparative multicentre study in general practice in the United Kingdom. Nifedipine-Atenolol Study Review Committee. BMJ. 1988; 296(6620):468–72 [<a href="/pmc/articles/PMC2545049/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2545049</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/2894883" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2894883</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>11.</dt><dd><div class="bk_ref" id="ch5.ref11">Aoki
|
|
K, Kondo
|
|
S, Mochizuki
|
|
A, Yoshida
|
|
T, Kato
|
|
S, Kato
|
|
K
|
|
et al. Antihypertensive effect of cardiovascular Ca<sup>2+</sup>-antagonist in hypertensive patients in the absence and presence of beta-adrenergic blockade. American Heart Journal. 1978; 96(2):218–26 [<a href="https://pubmed.ncbi.nlm.nih.gov/676983" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 676983</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>12.</dt><dd><div class="bk_ref" id="ch5.ref12">Applegate
|
|
W, Cohen
|
|
JD, Wolfson
|
|
P, Davis
|
|
A, Green
|
|
S. Long-term effectiveness of enalapril plus extended-release diltiazem in essential hypertension. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 1997; 17(1):107–12 [<a href="https://pubmed.ncbi.nlm.nih.gov/9017770" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9017770</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>13.</dt><dd><div class="bk_ref" id="ch5.ref13">Asmar
|
|
RG, London
|
|
GM, O’Rourke
|
|
ME, Mallion
|
|
JM, Romero
|
|
R, Rahn
|
|
KH
|
|
et al. Amelioration of arterial properties with a perindopril-indapamide very-low-dose combination. Journal of Hypertension Supplement. 2001; 19(4):S15–20 [<a href="https://pubmed.ncbi.nlm.nih.gov/11848258" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11848258</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>14.</dt><dd><div class="bk_ref" id="ch5.ref14">Asmar
|
|
RG, London
|
|
GM, O’Rourke
|
|
ME, Safar
|
|
ME, Reason Project Coordinators and Investigators. Improvement in blood pressure, arterial stiffness and wave reflections with a very-low-dose perindopril/indapamide combination in hypertensive patient: A comparison with atenolol. Hypertension. 2001; 38(4):922–6 [<a href="https://pubmed.ncbi.nlm.nih.gov/11641310" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11641310</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>15.</dt><dd><div class="bk_ref" id="ch5.ref15">Bakris
|
|
G, Briasoulis
|
|
A, Dahlof
|
|
B, Jamerson
|
|
K, Weber
|
|
MA, Kelly
|
|
RY
|
|
et al. Comparison of benazepril plus amlodipine or hydrochlorothiazide in high-risk patients with hypertension and coronary artery disease. American Journal of Cardiology. 2013; 112(2):255–9 [<a href="https://pubmed.ncbi.nlm.nih.gov/23582626" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23582626</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>16.</dt><dd><div class="bk_ref" id="ch5.ref16">Basile
|
|
J, Babazadeh
|
|
S, Lillestol
|
|
M, Botha
|
|
J, Yurkovic
|
|
C, Weitzman
|
|
R. Comparison of aliskiren/hydrochlorothiazide combination therapy with hydrochlorothiazide monotherapy in older patients with stage 2 systolic hypertension: Results of the ACTION study. Journal of Clinical Hypertension. 2011; 13(3):162–9 [<a href="/pmc/articles/PMC8673033/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8673033</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21366847" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21366847</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>17.</dt><dd><div class="bk_ref" id="ch5.ref17">Bays
|
|
H, Zhu
|
|
D, Schumacher
|
|
H. Single-pill combination of telmisartan and hydrochlorothiazide: Studies and pooled analyses of earlier hypertension treatment. High Blood Pressure & Cardiovascular Prevention. 2014; 21(2):119–26 [<a href="https://pubmed.ncbi.nlm.nih.gov/24493330" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24493330</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>18.</dt><dd><div class="bk_ref" id="ch5.ref18">Benedict Group. The BErgamo NEphrologic DIabetes Complications Trial (BENEDICT): Design and baseline characteristics. Controlled Clinical Trials. 2003; 24(4):442–61 [<a href="https://pubmed.ncbi.nlm.nih.gov/12865039" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12865039</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>19.</dt><dd><div class="bk_ref" id="ch5.ref19">Benjamin
|
|
N, Phillips
|
|
RJ, Robinson
|
|
BF. Verapamil and bendrofluazide in the treatment of hypertension: A controlled study of effectiveness alone and in combination. European Journal of Clinical Pharmacology. 1988; 34(3):249–53 [<a href="https://pubmed.ncbi.nlm.nih.gov/3294021" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3294021</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>20.</dt><dd><div class="bk_ref" id="ch5.ref20">Bennett
|
|
A, Chow
|
|
CK, Chou
|
|
M, Dehbi
|
|
HM, Webster
|
|
R, Salam
|
|
A
|
|
et al. Efficacy and safety of quarter-dose blood pressure-lowering agents: A systematic review and meta-analysis of randomized controlled trials. Hypertension. 2017; 70(1):85–93 [<a href="https://pubmed.ncbi.nlm.nih.gov/28584013" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28584013</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>21.</dt><dd><div class="bk_ref" id="ch5.ref21">Beretta-Piccoli
|
|
C, Amstein
|
|
R, Bertel
|
|
O, Brunner
|
|
HR, Buhler
|
|
FR, Follath
|
|
F
|
|
et al. Antihypertensive efficacy of ketanserin alone or in combination with a beta-blocker or a diuretic: The Swiss Ketanserin Study. Journal of Cardiovascular Pharmacology. 1987; 10:(Suppl 3):S119–23 [<a href="https://pubmed.ncbi.nlm.nih.gov/2446058" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2446058</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>22.</dt><dd><div class="bk_ref" id="ch5.ref22">Bielmann
|
|
P, Leduc
|
|
G, Thibault
|
|
G, Lepage
|
|
J, Davignon
|
|
J. Effects of chlortalidone and metoprolol alone or in combination (logroton) on blood pressure, lipids, lipoproteins and circulating plasma ANF levels in essential hypertension. International Journal of Clinical Pharmacology, Therapy, and Toxicology. 1991; 29(12):479–85 [<a href="https://pubmed.ncbi.nlm.nih.gov/1839902" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1839902</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>23.</dt><dd><div class="bk_ref" id="ch5.ref23">Black
|
|
HR, Davis
|
|
B, Barzilay
|
|
J, Nwachuku
|
|
C, Baimbridge
|
|
C, Marginean
|
|
H
|
|
et al. Metabolic and clinical outcomes in nondiabetic individuals with the metabolic syndrome assigned to chlortalidone, amlodipine, or lisinopril as initial treatment for hypertension: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Diabetes Care. 2008; 31(2):353–60 [<a href="https://pubmed.ncbi.nlm.nih.gov/18000186" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18000186</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>24.</dt><dd><div class="bk_ref" id="ch5.ref24">Black
|
|
HR, Elliott
|
|
WJ, Grandits
|
|
G, Grambsch
|
|
P, Lucente
|
|
T, Neaton
|
|
JD
|
|
et al. Results of the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) trial by geographical region. Journal of Hypertension. 2005; 23(5):1099–106 [<a href="https://pubmed.ncbi.nlm.nih.gov/15834298" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15834298</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>25.</dt><dd><div class="bk_ref" id="ch5.ref25">Black
|
|
HR, Elliott
|
|
WJ, Grandits
|
|
G, Grambsch
|
|
P, Lucente
|
|
T, White
|
|
WB
|
|
et al. Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. JAMA. 2003; 289(16):2073–2082 [<a href="https://pubmed.ncbi.nlm.nih.gov/12709465" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12709465</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>26.</dt><dd><div class="bk_ref" id="ch5.ref26">Black
|
|
HR, Elliott
|
|
WJ, Neaton
|
|
JD, Grandits
|
|
G, Grambsch
|
|
P, Grimm
|
|
RH
|
|
et al. Rationale and design for the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Trial. Controlled Clinical Trials. 1998; 19(4):370–390 [<a href="https://pubmed.ncbi.nlm.nih.gov/9683312" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9683312</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>27.</dt><dd><div class="bk_ref" id="ch5.ref27">BMJ Group and the Royal Pharmaceutical Society of Great Britain. British National Formulary. Available from: <a href="https://www.evidence.nhs.uk/formulary/bnf/current" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://www<wbr style="display:inline-block"></wbr>​.evidence<wbr style="display:inline-block"></wbr>​.nhs.uk/formulary/bnf/current</a> Last accessed: 08 November 2018</div></dd></dl><dl class="bkr_refwrap"><dt>28.</dt><dd><div class="bk_ref" id="ch5.ref28">Bohm
|
|
M, Schumacher
|
|
H, Teo
|
|
KK, Lonn
|
|
EM, Mahfoud
|
|
F, Mann
|
|
JFE
|
|
et al. Achieved blood pressure and cardiovascular outcomes in high-risk patients: Results from ONTARGET and TRANSCEND trials. Lancet. 2017; 389(10085):2226–2237 [<a href="https://pubmed.ncbi.nlm.nih.gov/28390695" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28390695</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>29.</dt><dd><div class="bk_ref" id="ch5.ref29">Bomback
|
|
AS, Rekhtman
|
|
Y, Klemmer
|
|
PJ, Canetta
|
|
PA, Radhakrishnan
|
|
J, Appel
|
|
GB. Aldosterone breakthrough during aliskiren, valsartan, and combination (aliskiren + valsartan) therapy. Journal of the American Society of Hypertension. 2012; 6(5):338–45 [<a href="https://pubmed.ncbi.nlm.nih.gov/22995802" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22995802</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>30.</dt><dd><div class="bk_ref" id="ch5.ref30">Bradley
|
|
WF. A long-term clinical trial of prazosin. Postgraduate Medicine. 1975; Special:95–9 [<a href="https://pubmed.ncbi.nlm.nih.gov/1105491" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1105491</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>31.</dt><dd><div class="bk_ref" id="ch5.ref31">Breithaupt-Grogler
|
|
K, Gerhardt
|
|
G, Lehmann
|
|
G, Notter
|
|
T, Belz
|
|
GG. Blood pressure and aortic elastic properties: Verapamil SR/trandolapril compared to a metoprolol/hydrochlorothiazide combination therapy. International Journal of Clinical Pharmacology and Therapeutics. 1998; 36(8):425–31 [<a href="https://pubmed.ncbi.nlm.nih.gov/9726695" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9726695</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>32.</dt><dd><div class="bk_ref" id="ch5.ref32">Bremner
|
|
AD, Baur
|
|
M, Oddou-Stock
|
|
P, Bodin
|
|
F. Valsartan: Long-term efficacy and tolerability compared to lisinopril in elderly patients with essential hypertension. Clinical and Experimental Hypertension. 1997; 19(8):1263–1285 [<a href="https://pubmed.ncbi.nlm.nih.gov/9385475" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9385475</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>33.</dt><dd><div class="bk_ref" id="ch5.ref33">Bremner
|
|
AD, Mehring
|
|
GH, Meilenbrock
|
|
S. Long-term systemic tolerability of valsartan compared with lisinopril in elderly hypertensive patients. Advances in Therapy. 1997; 14(5):245–253</div></dd></dl><dl class="bkr_refwrap"><dt>34.</dt><dd><div class="bk_ref" id="ch5.ref34">Brown
|
|
MJ, Palmer
|
|
CR, Castaigne
|
|
A, de Leeuw
|
|
PW, Mancia
|
|
G, Rosenthal
|
|
T
|
|
et al. Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). The Lancet. 2000; 356(9227):366–72 [<a href="https://pubmed.ncbi.nlm.nih.gov/10972368" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10972368</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>35.</dt><dd><div class="bk_ref" id="ch5.ref35">Brown
|
|
MJ, Palmer
|
|
CR, Castaigne
|
|
A, De Leeuw
|
|
PW, Mancia
|
|
G, Rosenthal
|
|
T
|
|
et al. Principal results from the international nifedipine GITS Study: Intervention as a goal in hypertension treatment (INSIGHT). European Heart Journal, Supplement. 2001; 3(Suppl B):B20–B26</div></dd></dl><dl class="bkr_refwrap"><dt>36.</dt><dd><div class="bk_ref" id="ch5.ref36">Brown
|
|
MJ, Struthers
|
|
AD, Di Silvio
|
|
L. Metabolic and haemodynamic effects of alpha2-adrenoceptor stimulation and antagonism in man. Clinical Science. 1985; 68:(Suppl 10):137S–139S [<a href="https://pubmed.ncbi.nlm.nih.gov/2857610" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2857610</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>37.</dt><dd><div class="bk_ref" id="ch5.ref37">Brown
|
|
MJ, Toal
|
|
CB. Formulation of long-acting nifedipine tablets influences the heart rate and sympathetic nervous system response in hypertensive patients. British Journal of Clinical Pharmacology. 2008; 65(5):646–652 [<a href="/pmc/articles/PMC2432473/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2432473</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18093252" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18093252</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>38.</dt><dd><div class="bk_ref" id="ch5.ref38">Brown
|
|
MJ, Williams
|
|
B, MacDonald
|
|
TM, Caulfield
|
|
M, Cruickshank
|
|
JK, McInnes
|
|
G
|
|
et al. Comparison of single and combination diuretics on glucose tolerance (PATHWAY-3): Protocol for a randomised double-blind trial in patients with essential hypertension. BMJ Open. 2015; 5(8):e008086 [<a href="/pmc/articles/PMC4539390/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4539390</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26253567" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26253567</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>39.</dt><dd><div class="bk_ref" id="ch5.ref39">Chalmers
|
|
J. Efficacy and acceptability of the fixed low-dose perindopril-indapamide combination as first-line therapy in hypertension. European Heart Journal, Supplement. 1999; 1(Suppl L):L20–L25</div></dd></dl><dl class="bkr_refwrap"><dt>40.</dt><dd><div class="bk_ref" id="ch5.ref40">Chaugai
|
|
S, Sherpa
|
|
LY, Sepehry
|
|
AA, Kerman
|
|
SRJ, Arima
|
|
H. Effects of long- and intermediate-acting dihydropyridine calcium channel blockers in hypertension: A systematic review and meta-analysis of 18 prospective, randomized, actively controlled trials. Journal of Cardiovascular Pharmacology and Therapeutics. 2018; 23(5):433–445 [<a href="https://pubmed.ncbi.nlm.nih.gov/29739234" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29739234</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>41.</dt><dd><div class="bk_ref" id="ch5.ref41">Chung
|
|
JW, Lee
|
|
HY, Kim
|
|
CH, Seung
|
|
IW, Shin
|
|
YW, Jeong
|
|
MH
|
|
et al. Losartan/hydrochlorothiazide fixed combination versus amlodipine monotherapy in Korean patients with mild to moderate hypertension. Korean Circulation Journal. 2009; 39(4):151–6 [<a href="/pmc/articles/PMC2771809/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2771809</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19949604" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19949604</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>42.</dt><dd><div class="bk_ref" id="ch5.ref42">Ciulla
|
|
MM, Paliotti
|
|
R, Esposito
|
|
A, Cuspidi
|
|
C, Muiesan
|
|
ML, Rosei
|
|
EA
|
|
et al. Effects of antihypertensive treatment on ultrasound measures of myocardial fibrosis in hypertensive patients with left ventricular hypertrophy: Results of a randomized trial comparing the angiotensin receptor antagonist, candesartan and the angiotensin-converting enzyme inhibitor, enalapril. Journal of Hypertension. 2009; 27(3):626–32 [<a href="https://pubmed.ncbi.nlm.nih.gov/19262230" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19262230</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>43.</dt><dd><div class="bk_ref" id="ch5.ref43">Ciulla
|
|
MM, Paliotti
|
|
R, Esposito
|
|
A, Dìez
|
|
J, López
|
|
B, Dahlöf
|
|
B
|
|
et al. Different effects of antihypertensive therapies based on losartan or atenolol on ultrasound and biochemical markers of myocardial fibrosis: Results of a randomized trial. Circulation. 2004; 110(5):552–557 [<a href="https://pubmed.ncbi.nlm.nih.gov/15277331" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15277331</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>44.</dt><dd><div class="bk_ref" id="ch5.ref44">Cushman
|
|
WC, Cohen
|
|
JD, Jones
|
|
RP, Marbury
|
|
TC, Rhoades
|
|
RB, Smith
|
|
LK. Comparison of the fixed combination of enalapril/diltiazem ER and their monotherapies in stage 1 to 3 essential hypertension. American Journal of Hypertension. 1998; 11(1 Pt 1):23–30 [<a href="https://pubmed.ncbi.nlm.nih.gov/9504446" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9504446</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>45.</dt><dd><div class="bk_ref" id="ch5.ref45">Dafgard
|
|
T, Forsen
|
|
B, Lindahl
|
|
T. Comparative study of hydrochlorothiazide and a fixed combination of metoprolol and hydrochlorothiazide essential hypertension. Annals of Clinical Research. 1981; 13:(Suppl 30):37–44 [<a href="https://pubmed.ncbi.nlm.nih.gov/7027892" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7027892</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>46.</dt><dd><div class="bk_ref" id="ch5.ref46">Dahlöf
|
|
B, Andrén
|
|
L, Eggertsen
|
|
R, Jern
|
|
S, Svensson
|
|
A, Hansson
|
|
L. The long-term effect of isradipine in pindolol-treated patients. Journal of Hypertension Supplement. 1987; 5(5):S567–70 [<a href="https://pubmed.ncbi.nlm.nih.gov/2965231" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2965231</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>47.</dt><dd><div class="bk_ref" id="ch5.ref47">Dahlof
|
|
B, Gosse
|
|
P, Gueret
|
|
P, Dubourg
|
|
O, de Simone
|
|
G, Schmieder
|
|
R
|
|
et al. Perindopril/indapamide combination more effective than enalapril in reducing blood pressure and left ventricular mass: The PICXEL study. Journal of Hypertension. 2005; 23(11):2063–70 [<a href="https://pubmed.ncbi.nlm.nih.gov/16208150" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16208150</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>48.</dt><dd><div class="bk_ref" id="ch5.ref48">Dahlöf
|
|
B, Sever
|
|
PS, Poulter
|
|
NR, Wedel
|
|
H, Beevers
|
|
DG, Caulfield
|
|
M
|
|
et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): A multicentre randomised controlled trial. The Lancet. 2005; 366(9489):895–906 [<a href="https://pubmed.ncbi.nlm.nih.gov/16154016" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16154016</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>49.</dt><dd><div class="bk_ref" id="ch5.ref49">Damian
|
|
DJ, McNamee
|
|
R, Carr
|
|
M. Changes in selected metabolic parameters in patients over 65 receiving hydrochlorothiazide plus amiloride, atenolol or placebo in the MRC elderly trial. BMC Cardiovascular Disorders. 2016; 16:188 [<a href="/pmc/articles/PMC5050956/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5050956</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27716064" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27716064</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>50.</dt><dd><div class="bk_ref" id="ch5.ref50">de Divitiis
|
|
O, Petitto
|
|
M, Di Somma
|
|
S, Fazio
|
|
S, Galderisi
|
|
M, Villari
|
|
B
|
|
et al. Acebutolol and nifedipine in the treatment of arterial hypertension: Efficacy and acceptability. Arzneimittel-Forschung. 1984; 34(6):710–5 [<a href="https://pubmed.ncbi.nlm.nih.gov/6386007" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6386007</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>51.</dt><dd><div class="bk_ref" id="ch5.ref51">de Galan
|
|
BE, Perkovic
|
|
V, Ninomiya
|
|
T, Pillai
|
|
A, Patel
|
|
A, Cass
|
|
A
|
|
et al. Lowering blood pressure reduces renal events in type 2 diabetes. Journal of the American Society of Nephrology. 2009; 20(4):883–92 [<a href="/pmc/articles/PMC2663832/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2663832</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19225038" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19225038</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>52.</dt><dd><div class="bk_ref" id="ch5.ref52">de Luca
|
|
N, Asmar
|
|
RG, London
|
|
GM, O’Rourke
|
|
MF, Safar
|
|
ME, Reason Project Investigators. Selective reduction of cardiac mass and central blood pressure on low-dose combination perindopril/indapamide in hypertensive subjects. Journal of Hypertension. 2004; 22(8):1623–30 [<a href="https://pubmed.ncbi.nlm.nih.gov/15257187" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15257187</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>53.</dt><dd><div class="bk_ref" id="ch5.ref53">Degl’Innocenti
|
|
A, Elmfeldt
|
|
D, Hofman
|
|
A, Lithell
|
|
H, Olofsson
|
|
B, Skoog
|
|
I
|
|
et al. Health-related quality of life during treatment of elderly patients with hypertension: Results from the Study on COgnition and Prognosis in the Elderly (SCOPE). Journal of Human Hypertension. 2004; 18(4):239–245 [<a href="https://pubmed.ncbi.nlm.nih.gov/15037872" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15037872</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>54.</dt><dd><div class="bk_ref" id="ch5.ref54">Delea
|
|
TE, Sofrygin
|
|
O, Palmer
|
|
JL, Lau
|
|
H, Munk
|
|
VC, Sung
|
|
J
|
|
et al. Cost-effectiveness of aliskiren in type 2 diabetes, hypertension, and albuminuria. Journal of the American Society of Nephrology. 2009; 20(10):2205–2213 [<a href="/pmc/articles/PMC2754109/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2754109</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19762496" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19762496</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>55.</dt><dd><div class="bk_ref" id="ch5.ref55">Department of Health. NHS reference costs 2016–17. 2017. Available from: <a href="https://improvement.nhs.uk/resources/reference-costs/#archive" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://improvement<wbr style="display:inline-block"></wbr>​.nhs<wbr style="display:inline-block"></wbr>​.uk/resources/reference-costs<wbr style="display:inline-block"></wbr>​/#archive</a> Last accessed: 03/01/19</div></dd></dl><dl class="bkr_refwrap"><dt>56.</dt><dd><div class="bk_ref" id="ch5.ref56">DeQuattro
|
|
V, Lee
|
|
D. Fixed-dose combination therapy with trandolapril and verapamil SR is effective in primary hypertension. Trandolapril Study Group. American Journal of Hypertension. 1997; 10(7 Pt 2):138S–145S [<a href="https://pubmed.ncbi.nlm.nih.gov/9231890" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9231890</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>57.</dt><dd><div class="bk_ref" id="ch5.ref57">DeQuattro
|
|
V, Lee
|
|
D, Messerli
|
|
F, The Trandolapril Study Group. Efficacy of combination therapy with trandolapril and verapamil sr in primary hypertension: A 4 × 4 trial design. Clinical and Experimental Hypertension. 1997; 19(3):373–87 [<a href="https://pubmed.ncbi.nlm.nih.gov/9107443" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9107443</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>58.</dt><dd><div class="bk_ref" id="ch5.ref58">Derosa
|
|
G, Bonaventura
|
|
A, Romano
|
|
D, Bianchi
|
|
L, Fogari
|
|
E, D’Angelo
|
|
A
|
|
et al. Effects of enalapril/lercanidipine combination on some emerging biomarkers in cardiovascular risk stratification in hypertensive patients. Journal of Clinical Pharmacy and Therapeutics. 2014; 39(3):277–85 [<a href="https://pubmed.ncbi.nlm.nih.gov/24635387" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24635387</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>59.</dt><dd><div class="bk_ref" id="ch5.ref59">Derosa
|
|
G, Cicero
|
|
AF, Carbone
|
|
A, Querci
|
|
F, Fogari
|
|
E, D’Angelo
|
|
A
|
|
et al. Effects of an olmesartan/amlodipine fixed dose on blood pressure control, some adipocytokines and interleukins levels compared with olmesartan or amlodipine monotherapies. Journal of Clinical Pharmacy and Therapeutics. 2013; 38(1):48–55 [<a href="https://pubmed.ncbi.nlm.nih.gov/23216584" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23216584</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>60.</dt><dd><div class="bk_ref" id="ch5.ref60">Derosa
|
|
G, Cicero
|
|
AF, Carbone
|
|
A, Querci
|
|
F, Fogari
|
|
E, D’Angelo
|
|
A
|
|
et al. Olmesartan/amlodipine combination versus olmesartan or amlodipine monotherapies on blood pressure and insulin resistance in a sample of hypertensive patients. Clinical and Experimental Hypertension. 2013; 35(5):301–7 [<a href="https://pubmed.ncbi.nlm.nih.gov/22954201" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22954201</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>61.</dt><dd><div class="bk_ref" id="ch5.ref61">Derosa
|
|
G, Cicero
|
|
AF, Carbone
|
|
A, Querci
|
|
F, Fogari
|
|
E, D’Angelo
|
|
A
|
|
et al. Variation of some inflammatory markers in hypertensive patients after 1 year of olmesartan/amlodipine single-pill combination compared with olmesartan or amlodipine monotherapies. Journal of the American Society of Hypertension. 2013; 7(1):32–9 [<a href="https://pubmed.ncbi.nlm.nih.gov/23321403" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23321403</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>62.</dt><dd><div class="bk_ref" id="ch5.ref62">Derosa
|
|
G, Cicero
|
|
AF, Carbone
|
|
A, Querci
|
|
F, Fogari
|
|
E, D’Angelo
|
|
A
|
|
et al. Different aspects of sartan + calcium antagonist association compared to the single therapy on inflammation and metabolic parameters in hypertensive patients. Inflammation. 2014; 37(1):154–62 [<a href="https://pubmed.ncbi.nlm.nih.gov/24018781" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24018781</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>63.</dt><dd><div class="bk_ref" id="ch5.ref63">Derosa
|
|
G, Cicero
|
|
AF, Carbone
|
|
A, Querci
|
|
F, Fogari
|
|
E, D’Angelo
|
|
A
|
|
et al. Results from a 12 months, randomized, clinical trial comparing an olmesartan/amlodipine single pill combination to olmesartan and amlodipine monotherapies on blood pressure and inflammation. European Journal of Pharmaceutical Sciences. 2014; 51:26–33 [<a href="https://pubmed.ncbi.nlm.nih.gov/23999037" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23999037</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>64.</dt><dd><div class="bk_ref" id="ch5.ref64">Derosa
|
|
G, Mugellini
|
|
A, Pesce
|
|
RM, D’Angelo
|
|
A, Maffioli
|
|
P. Perindopril and barnidipine alone or combined with simvastatin on hepatic steatosis and inflammatory parameters in hypertensive patients. European Journal of Pharmacology. 2015; 766:31–6 [<a href="https://pubmed.ncbi.nlm.nih.gov/26407654" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26407654</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>65.</dt><dd><div class="bk_ref" id="ch5.ref65">Derosa
|
|
G, Mugellini
|
|
A, Pesce
|
|
RM, D’Angelo
|
|
A, Maffioli
|
|
P. Olmesartan combined with amlodipine on oxidative stress parameters in type 2 diabetics, compared with single therapies: A randomized, controlled, clinical trial. Medicine. 2016; 95(13):e3084 [<a href="/pmc/articles/PMC4998532/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4998532</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27043671" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27043671</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>66.</dt><dd><div class="bk_ref" id="ch5.ref66">Destro
|
|
M, Luckow
|
|
A, Samson
|
|
M, Kandra
|
|
A, Brunel
|
|
P. Efficacy and safety of amlodipine/valsartan compared with amlodipine monotherapy in patients with stage 2 hypertension: A randomized, double-blind, multicenter study: The EX-EFFeCTS Study. Journal of the American Society of Hypertension. 2008; 2(4):294–302 [<a href="https://pubmed.ncbi.nlm.nih.gov/20409909" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20409909</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>67.</dt><dd><div class="bk_ref" id="ch5.ref67">Dickson
|
|
M, Plauschinat
|
|
CA. Compliance with antihypertensive therapy in the elderly: A comparison of fixed-dose combination amlodipine/benazepril versus component-based free-combination therapy. American Journal of Cardiovascular Drugs. 2008; 8(1):45–50 [<a href="https://pubmed.ncbi.nlm.nih.gov/18303937" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18303937</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>68.</dt><dd><div class="bk_ref" id="ch5.ref68">Drayer
|
|
JI, Stimpel
|
|
M, Fox
|
|
A, Weber
|
|
M. The antihypertensive properties of the angiotensin-converting enzyme inhibitor moexipril given alone or in combination with a low dose of a diuretic. American Journal of Therapeutics. 1995; 2(8):525–531 [<a href="https://pubmed.ncbi.nlm.nih.gov/11854821" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11854821</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>69.</dt><dd><div class="bk_ref" id="ch5.ref69">Duckett
|
|
GK, Cheadle
|
|
B. Hypertension in the elderly: A study of a combination of atenolol and nifedipine. British Journal of Clinical Practice. 1990; 44(2):52–4 [<a href="https://pubmed.ncbi.nlm.nih.gov/2200490" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2200490</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>70.</dt><dd><div class="bk_ref" id="ch5.ref70">Dzurik
|
|
R, Fetkovska
|
|
N, Dvorak
|
|
I, Jonas
|
|
P, Markuljak
|
|
I, Petr
|
|
P
|
|
et al. Isradipine in monotherapy and in combination with bopindolol: Results of a 3-month multicentre study in hypertensives. Cor et Vasa. 1990; 32(2 Suppl 1):42–53 [<a href="https://pubmed.ncbi.nlm.nih.gov/1974488" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1974488</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>71.</dt><dd><div class="bk_ref" id="ch5.ref71">El-Mehairy
|
|
MM, Shaker
|
|
A, Ramadan
|
|
M, Hamza
|
|
S, Tadros
|
|
SS. Long-term treatment of essential hypertension using nadolol and hydrochlorothiazide combined. British Journal of Clinical Pharmacology. 1979; 7:(Suppl 2):199S–203S [<a href="/pmc/articles/PMC1429333/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1429333</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/37875" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37875</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>72.</dt><dd><div class="bk_ref" id="ch5.ref72">Elliott
|
|
HL, Meredith
|
|
PA, Campbell
|
|
L, Reid
|
|
JL. The combination of prazosin and verapamil in the treatment of essential hypertension. Clinical Pharmacology and Therapeutics. 1988; 43(5):554–60 [<a href="https://pubmed.ncbi.nlm.nih.gov/3284690" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3284690</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>73.</dt><dd><div class="bk_ref" id="ch5.ref73">Family Physicians Hypertension Study Group, Cajochen
|
|
C, Krauchi
|
|
K, Von
|
|
AMA, Mori
|
|
D, Graw
|
|
P
|
|
et al. A multicenter comparison of the antihypertensive effects of atenolol and chlortalidone given alone and in combination. Current Therapeutic Research, Clinical and Experimental. 1984; 35(1):31–39</div></dd></dl><dl class="bkr_refwrap"><dt>74.</dt><dd><div class="bk_ref" id="ch5.ref74">Fang
|
|
H, Chen
|
|
W, Liu
|
|
X, Xu
|
|
W. The efficacy and safety of arotinolol combined with a different calcium channel blocker in the treatment of Chinese patients with essential hypertension: A one-year follow-up study. Clinical and Experimental Hypertension. 2014; 36(8):590–5 [<a href="https://pubmed.ncbi.nlm.nih.gov/24678807" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24678807</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>75.</dt><dd><div class="bk_ref" id="ch5.ref75">Feldman
|
|
RD, Zou
|
|
GY, Vandervoort
|
|
MK, Wong
|
|
CJ, Nelson
|
|
SA, Feagan
|
|
BG. A simplified approach to the treatment of uncomplicated hypertension: A cluster randomized, controlled trial. Hypertension. 2009; 53(4):646–53 [<a href="https://pubmed.ncbi.nlm.nih.gov/19237683" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19237683</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>76.</dt><dd><div class="bk_ref" id="ch5.ref76">Fell
|
|
PJ. Long-term treatment of hypertension in the elderly with a combination of atenolol and nifedipine. Current Medical Research and Opinion. 1990; 12(1):66–70 [<a href="https://pubmed.ncbi.nlm.nih.gov/2188798" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2188798</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>77.</dt><dd><div class="bk_ref" id="ch5.ref77">Ferrari
|
|
R. Optimizing the treatment of hypertension and stable coronary artery disease: Clinical evidence for fixed-combination perindopril/amlodipine. Current Medical Research and Opinion. 2008; 24(12):3543–57 [<a href="https://pubmed.ncbi.nlm.nih.gov/19032136" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19032136</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>78.</dt><dd><div class="bk_ref" id="ch5.ref78">Fogari
|
|
R, Derosa
|
|
G, Zoppi
|
|
A, Preti
|
|
P, Lazzari
|
|
P, Destro
|
|
M
|
|
et al. Effect of telmisartan-amlodipine combination at different doses on urinary albumin excretion in hypertensive diabetic patients with microalbuminuria. American Journal of Hypertension. 2007; 20(4):417–22 [<a href="https://pubmed.ncbi.nlm.nih.gov/17386350" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17386350</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>79.</dt><dd><div class="bk_ref" id="ch5.ref79">Fogari
|
|
R, Preti
|
|
P, Zoppi
|
|
A, Rinaldi
|
|
A, Corradi
|
|
L, Pasotti
|
|
C
|
|
et al. Effects of amlodipine fosinopril combination on microalbuminuria in hypertensive type 2 diabetic patients. American Journal of Hypertension. 2002; 15(12):1042–9 [<a href="https://pubmed.ncbi.nlm.nih.gov/12460699" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12460699</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>80.</dt><dd><div class="bk_ref" id="ch5.ref80">Fogari
|
|
R, Zoppi
|
|
A, Mugellini
|
|
A, Preti
|
|
P, Destro
|
|
M, Rinaldi
|
|
A
|
|
et al. Effectiveness of hydrochlorothiazide in combination with telmisartan and olmesartan in adults with moderate hypertension not controlled with monotherapy: A prospective, randomized, open-label, blinded end point (PROBE), parallel-arm study. Current Therapeutic Research, Clinical and Experimental. 2008; 69(1):1–15 [<a href="/pmc/articles/PMC3969955/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3969955</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24692778" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24692778</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>81.</dt><dd><div class="bk_ref" id="ch5.ref81">Forette
|
|
F, Seux
|
|
ML, Staessen
|
|
JA, Thijs
|
|
L, Babarskiene
|
|
MR, Babeanu
|
|
S
|
|
et al. The prevention of dementia with antihypertensive treatment: New evidence from the Systolic Hypertension in Europe (Syst-Eur) study. Archives of Internal Medicine. 2002; 162(18):2046–2052 [<a href="https://pubmed.ncbi.nlm.nih.gov/12374512" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12374512</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>82.</dt><dd><div class="bk_ref" id="ch5.ref82">Franklin
|
|
SS, Weir
|
|
MR, Smith
|
|
DH, Codispoti
|
|
J, Stokes
|
|
A, McNally
|
|
C
|
|
et al. Combination treatment with sustained-release verapamil and indapamide in the treatment of mild-to-moderate hypertension. American Journal of Therapeutics. 1996; 3(7):506–514 [<a href="https://pubmed.ncbi.nlm.nih.gov/11862282" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11862282</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>83.</dt><dd><div class="bk_ref" id="ch5.ref83">Franz
|
|
IW, Tönnesmann
|
|
U, Behr
|
|
U, Ketelhut
|
|
R. Regression of left ventricular hypertrophy in hypertensive patients under long-term therapy with antihypertensive agents. Deutsche Medizinische Wochenschrift. 1990; 115(16):603–609 [<a href="https://pubmed.ncbi.nlm.nih.gov/2139409" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2139409</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>84.</dt><dd><div class="bk_ref" id="ch5.ref84">Freytag
|
|
F, Holwerda
|
|
NJ, Karlberg
|
|
BE, Meinicke
|
|
TW, Schumacher
|
|
H. Long-term exposure to telmisartan as monotherapy or combination therapy: Efficacy and safety. Blood Pressure. 2002; 11(3):173–81 [<a href="https://pubmed.ncbi.nlm.nih.gov/12126264" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12126264</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>85.</dt><dd><div class="bk_ref" id="ch5.ref85">Frishman
|
|
WH, Burris
|
|
JF, Mroczek
|
|
WJ, Weir
|
|
MR, Alemayehu
|
|
D, Simon
|
|
JS
|
|
et al. First-line therapy option with low-dose bisoprolol fumarate and low-dose hydrochlorothiazide in patients with stage I and stage II systemic hypertension. Journal of Clinical Pharmacology. 1995; 35(2):182–8 [<a href="https://pubmed.ncbi.nlm.nih.gov/7751430" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7751430</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>86.</dt><dd><div class="bk_ref" id="ch5.ref86">Fu
|
|
S, Wen
|
|
X, Han
|
|
F, Long
|
|
Y, Xu
|
|
G. Aliskiren therapy in hypertension and cardiovascular disease: a systematic review and a meta-analysis. Oncotarget. 2017; 8(51):89364–89374 [<a href="/pmc/articles/PMC5687695/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5687695</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29179525" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29179525</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>87.</dt><dd><div class="bk_ref" id="ch5.ref87">Fujisaki
|
|
K, Tsuruya
|
|
K, Nakano
|
|
T, Taniguchi
|
|
M, Higashi
|
|
H, Katafuchi
|
|
R
|
|
et al. Impact of combined losartan/hydrochlorothiazide on proteinuria in patients with chronic kidney disease and hypertension. Hypertension Research. 2014; 37(11):993–8 [<a href="https://pubmed.ncbi.nlm.nih.gov/24965167" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24965167</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>88.</dt><dd><div class="bk_ref" id="ch5.ref88">Garcia de Vinuesa
|
|
S, Luno
|
|
J, Gomez-Campdera
|
|
F, Ridao
|
|
N, Sanchez
|
|
M, Dall’Anese
|
|
C
|
|
et al. Effect of strict blood pressure control on proteinuria in renal patients treated with different antihypertensive drugs. Nephrology Dialysis Transplantation. 2001; 16:(Suppl 1):78–81 [<a href="https://pubmed.ncbi.nlm.nih.gov/11369828" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11369828</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>89.</dt><dd><div class="bk_ref" id="ch5.ref89">Garjon
|
|
J, Saiz
|
|
LC, Azparren
|
|
A, Elizondo
|
|
JJ, Gaminde
|
|
I, Ariz
|
|
MJ
|
|
et al. First-line combination therapy versus first-line monotherapy for primary hypertension. Cochrane Database of Systematic Reviews
|
|
2017, Issue 1. Art. No.: CD010316. DOI: 10.1002/14651858.CD010316.pub2. [<a href="/pmc/articles/PMC6464906/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6464906</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28084624" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28084624</span></a>] [<a href="http://dx.crossref.org/10.1002/14651858.CD010316.pub2" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">CrossRef</a>]</div></dd></dl><dl class="bkr_refwrap"><dt>90.</dt><dd><div class="bk_ref" id="ch5.ref90">Girerd
|
|
X, Giannattasio
|
|
C, Moulin
|
|
C, Safar
|
|
M, Mancia
|
|
G, Laurent
|
|
S. Regression of radial artery wall hypertrophy and improvement of carotid artery compliance after long-term antihypertensive treatment in elderly patients. Journal of the American College of Cardiology. 1998; 31(5):1064–73 [<a href="https://pubmed.ncbi.nlm.nih.gov/9562008" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9562008</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>91.</dt><dd><div class="bk_ref" id="ch5.ref91">Goodman
|
|
C, Rosendorff
|
|
C, Coull
|
|
A. Comparison of the antihypertensive effect of enalapril and propranolol in black South Africans. South African Medical Journal. 1985; 67(17):672–6 [<a href="https://pubmed.ncbi.nlm.nih.gov/2986300" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2986300</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>92.</dt><dd><div class="bk_ref" id="ch5.ref92">Goyal
|
|
J, Khan
|
|
ZY, Upadhyaya
|
|
P, Goyal
|
|
B, Jain
|
|
S. Comparative study of high dose mono-therapy of amlodipine or telmisartan, and their low dose combination in mild to moderate hypertension. Journal of Clinical and Diagnostic Research JCDR. 2014; 8(6):HC08–11 [<a href="/pmc/articles/PMC4129356/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4129356</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25121000" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25121000</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>93.</dt><dd><div class="bk_ref" id="ch5.ref93">Grassi
|
|
G, Mancia
|
|
G. Olmesartan medoxomil: As monotherapy and in combination treatment in hypertension. High Blood Pressure & Cardiovascular Prevention. 2010; 17(1):1–14</div></dd></dl><dl class="bkr_refwrap"><dt>94.</dt><dd><div class="bk_ref" id="ch5.ref94">Grimm
|
|
RH, Jr., Flack
|
|
JM, Schoenberger
|
|
JA, Gonzalez
|
|
NM, Liebson
|
|
PR. Alpha-blockade and thiazide treatment of hypertension. A double-blind randomized trail comparing doxazosin and hydrochlorothiazide. American Journal of Hypertension. 1996; 9(5):445–54 [<a href="https://pubmed.ncbi.nlm.nih.gov/8735175" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8735175</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>95.</dt><dd><div class="bk_ref" id="ch5.ref95">Gupta
|
|
AK, Dahlof
|
|
B, Dobson
|
|
J, Sever
|
|
PS, Wedel
|
|
H, Poulter
|
|
NR
|
|
et al. Determinants of new-onset diabetes among 19,257 hypertensive patients randomized in the Anglo-Scandinavian Cardiac Outcomes Trial - Blood Pressure Lowering Arm and the relative influence of antihypertensive medication. Diabetes Care. 2008; 31(5):982–8 [<a href="https://pubmed.ncbi.nlm.nih.gov/18235048" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18235048</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>96.</dt><dd><div class="bk_ref" id="ch5.ref96">Guyot
|
|
D, Lemarié
|
|
JC. Efficacy of Triatec in monotherapy and in combination with Lasilix in a French multicenter study. Revue du Praticien. 1990; 40:(18 Suppl):27–30, 35–8 [<a href="https://pubmed.ncbi.nlm.nih.gov/2143596" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2143596</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>97.</dt><dd><div class="bk_ref" id="ch5.ref97">Hall
|
|
J, Marbury
|
|
T, Gray
|
|
J, Chaudhery
|
|
S, Chen
|
|
S, James
|
|
D
|
|
et al. Long term safety, tolerability and efficacy of valsartan: Results from one and two year trials. Journal of Clinical Research. 1998; 1:147–159</div></dd></dl><dl class="bkr_refwrap"><dt>98.</dt><dd><div class="bk_ref" id="ch5.ref98">Hall
|
|
WD, Montoro
|
|
R, Littlejohn
|
|
T, Jain
|
|
A, Feliciano
|
|
N, Zheng
|
|
H. Efficacy and tolerability of valsartan in combination with hydrochlorothiazide in essential hypertension. Clinical Drug Investigation. 1998; 16(3):203–10 [<a href="https://pubmed.ncbi.nlm.nih.gov/18370541" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18370541</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>99.</dt><dd><div class="bk_ref" id="ch5.ref99">Harmankaya
|
|
O, Seber
|
|
S, Yilmaz
|
|
M. Combination of pentoxifylline with angiotensin converting enzyme inhibitors produces an additional reduction in microalbuminuria in hypertensive type 2 diabetic patients. Renal Failure. 2003; 25(3):465–70 [<a href="https://pubmed.ncbi.nlm.nih.gov/12803510" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12803510</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>100.</dt><dd><div class="bk_ref" id="ch5.ref100">Hasegawa
|
|
Y, Yamaguchi
|
|
T, Omae
|
|
T, Woodward
|
|
M, Chalmers
|
|
J. Effects of perindopril-based blood pressure lowering and of patient characteristics on the progression of silent brain infarct: The Perindopril Protection against Recurrent Stroke Study (PROGRESS) CT Substudy in Japan. Hypertension Research. 2004; 27(3):147–156 [<a href="https://pubmed.ncbi.nlm.nih.gov/15080373" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15080373</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>101.</dt><dd><div class="bk_ref" id="ch5.ref101">He
|
|
T, Liu
|
|
X, Li
|
|
Y, Liu
|
|
XY, Wu
|
|
QY, Liu
|
|
ML
|
|
et al. High-dose calcium channel blocker (CCB) monotherapy vs combination therapy of standard-dose CCBs and angiotensin receptor blockers for hypertension: A meta-analysis. Journal of Human Hypertension. 2017; 31(2):79–88 [<a href="https://pubmed.ncbi.nlm.nih.gov/27511478" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27511478</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>102.</dt><dd><div class="bk_ref" id="ch5.ref102">Heidbreder
|
|
D, Froer
|
|
KL, Bauer
|
|
B, Cairns
|
|
V, Breitstadt
|
|
A. Efficacy and safety of ramipril in combination with hydrochlorothiazide: Results of a long-term study. Journal of Cardiovascular Pharmacology. 1991; 18:(Suppl 2):S169–S173 [<a href="https://pubmed.ncbi.nlm.nih.gov/1725034" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1725034</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>103.</dt><dd><div class="bk_ref" id="ch5.ref103">Heidbreder
|
|
D, Froer
|
|
KL, Breitstadt
|
|
A, Cairns
|
|
V, Langley
|
|
A, Bender
|
|
N. Combination of ramipril and hydrochlorothiazide in the treatment of mild to moderate hypertension: Part 1--A double-blind, comparative, multicenter study in nonresponders to ramipril monotherapy. Clinical Cardiology. 1992; 15(12):904–10 [<a href="https://pubmed.ncbi.nlm.nih.gov/1473306" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1473306</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>104.</dt><dd><div class="bk_ref" id="ch5.ref104">Helmer
|
|
A, Slater
|
|
N, Smithgall
|
|
S. A Review of ACE Inhibitors and ARBs in black patients with hypertension. Annals of Pharmacotherapy. 2018; 52(11):1143–1151 [<a href="https://pubmed.ncbi.nlm.nih.gov/29808707" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29808707</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>105.</dt><dd><div class="bk_ref" id="ch5.ref105">Herlitz
|
|
H, Harris
|
|
K, Risler
|
|
T, Boner
|
|
G, Bernheim
|
|
J, Chanard
|
|
J
|
|
et al. The effects of an ACE inhibitor and a calcium antagonist on the progression of renal disease: The Nephros Study. Nephrology Dialysis Transplantation. 2001; 16(11):2158–65 [<a href="https://pubmed.ncbi.nlm.nih.gov/11682661" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11682661</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>106.</dt><dd><div class="bk_ref" id="ch5.ref106">Hersh
|
|
AD, Kelly
|
|
JG, Laher
|
|
MS, Carmody
|
|
M, Doyle
|
|
GD. Effect of hydrochlorothiazide on the pharmacokinetics of enalapril in hypertensive patients with varying renal function. Journal of Cardiovascular Pharmacology. 1996; 27(1):7–11 [<a href="https://pubmed.ncbi.nlm.nih.gov/8656661" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8656661</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>107.</dt><dd><div class="bk_ref" id="ch5.ref107">Hill
|
|
JF, Bulpitt
|
|
CJ, Fletcher
|
|
AE. Angiotensin converting enzyme inhibitors and quality of life: The European trial. Journal of Hypertension Supplement. 1985; 3(2):S91–4 [<a href="https://pubmed.ncbi.nlm.nih.gov/3003305" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3003305</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>108.</dt><dd><div class="bk_ref" id="ch5.ref108">Hilleman
|
|
DE, Ryschon
|
|
KL, Mohiuddin
|
|
SM, Wurdeman
|
|
RL. Fixed-dose combination vs monotherapy in hypertension: A meta-analysis evaluation. Journal of Human Hypertension. 1999; 13(7):477–83 [<a href="https://pubmed.ncbi.nlm.nih.gov/10449213" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10449213</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>109.</dt><dd><div class="bk_ref" id="ch5.ref109">Höfling
|
|
B, Häringer
|
|
E, Herrmann
|
|
W, Pieske
|
|
H, Pieske
|
|
R, Philippi
|
|
M. Therapy of mild to moderate hypertension. Efficacy and tolerance of Amlodipine in comparison with the combination nifedipine/mefruside. Fortschritte der Medizin. 1991; 109(15):327–330 [<a href="https://pubmed.ncbi.nlm.nih.gov/1830287" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1830287</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>110.</dt><dd><div class="bk_ref" id="ch5.ref110">Holzgreve
|
|
H. Combination versus monotherapy as initial treatment in hypertension. Herz. 2003; 28(8):725–32 [<a href="https://pubmed.ncbi.nlm.nih.gov/14689107" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14689107</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>111.</dt><dd><div class="bk_ref" id="ch5.ref111">Holzgreve
|
|
H, Distler
|
|
A, Michaelis
|
|
J, Philipp
|
|
T, Wellek
|
|
S. Verapamil versus hydrochlorothiazide in the treatment of hypertension: Results of long term double blind comparative trial. BMJ. 1989; 299:881–6 [<a href="/pmc/articles/PMC1837749/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1837749</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/2510877" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2510877</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>112.</dt><dd><div class="bk_ref" id="ch5.ref112">Home
|
|
PD, Pocock
|
|
SJ, Beck-Nielsen
|
|
H, Curtis
|
|
PS, Gomis
|
|
R, Hanefeld
|
|
M
|
|
et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): A multicentre, randomised, open-label trial. The Lancet. 2009; 373(9681):2125–2135 [<a href="https://pubmed.ncbi.nlm.nih.gov/19501900" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19501900</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>113.</dt><dd><div class="bk_ref" id="ch5.ref113">Ihm
|
|
SH, Jeon
|
|
HK, Cha
|
|
TJ, Hong
|
|
TJ, Kim
|
|
SH, Lee
|
|
NH
|
|
et al. Efficacy and safety of two fixed-dose combinations of S-amlodipine and telmisartan (CKD-828) versus S-amlodipine monotherapy in patients with hypertension inadequately controlled using S-amlodipine monotherapy: An 8-week, multicenter, randomized, double-blind, phase III clinical study. Drug Design, Development and Therapy. 2016; 10:3817–3826 [<a href="/pmc/articles/PMC5125808/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5125808</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27920497" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27920497</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>114.</dt><dd><div class="bk_ref" id="ch5.ref114">Ishimitsu
|
|
T, Yagi
|
|
S, Ebihara
|
|
A, Doi
|
|
Y, Domae
|
|
A, Shibata
|
|
A
|
|
et al. Long-term evaluation of combined antihypertensive therapy with lisinopril and a thiazide diuretic in patients with essential hypertension. Japanese Heart Journal. 1997; 38(6):831–40 [<a href="https://pubmed.ncbi.nlm.nih.gov/9486936" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9486936</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>115.</dt><dd><div class="bk_ref" id="ch5.ref115">Jang
|
|
JY, Lee
|
|
SH, Kim
|
|
BS, Seo
|
|
HS, Kim
|
|
WS, Ahn
|
|
Y
|
|
et al. Additive beneficial effects of valsartan combined with rosuvastatin in the treatment of hypercholesterolemic hypertensive patients. Korean Circulation Journal. 2015; 45(3):225–33 [<a href="/pmc/articles/PMC4446817/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4446817</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26023311" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26023311</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>116.</dt><dd><div class="bk_ref" id="ch5.ref116">Johnson
|
|
BA, Roache
|
|
JD, Ait-Daoud
|
|
N, Wallace
|
|
C, Wells
|
|
LT, Wang
|
|
Y. Effects of isradipine on methamphetamine-induced changes in attentional and perceptual-motor skills of cognition. Psychopharmacology. 2005; 178(2–3):296–302 [<a href="https://pubmed.ncbi.nlm.nih.gov/15452681" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15452681</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>117.</dt><dd><div class="bk_ref" id="ch5.ref117">Johnson
|
|
BF, Johnson
|
|
J, Surve
|
|
A, Smith
|
|
H. The interaction of hydrochlorothiazide with spirapril: A novel ace inhibitor. American Journal of Therapeutics. 1994; 1(1):4–7 [<a href="https://pubmed.ncbi.nlm.nih.gov/11835060" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11835060</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>118.</dt><dd><div class="bk_ref" id="ch5.ref118">Katayama
|
|
K, Nomura
|
|
S, Ishikawa
|
|
H, Murata
|
|
T, Koyabu
|
|
S, Nakano
|
|
T. Comparison between valsartan and valsartan plus cilnidipine in type II diabetics with normo- and microalbuminuria. Kidney International. 2006; 70(1):151–156 [<a href="https://pubmed.ncbi.nlm.nih.gov/16710356" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16710356</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>119.</dt><dd><div class="bk_ref" id="ch5.ref119">Kato
|
|
H, Shiraishi
|
|
T, Ueda
|
|
S, Kubo
|
|
E, Shima
|
|
T, Nagura
|
|
M
|
|
et al. Blood pressure control and satisfaction of hypertensive patients following a switch to combined drugs of an angiotensin receptor blocker and a calcium channel blocker in clinical practice of nephrology. Clinical and Experimental Nephrology. 2015; 19(3):465–73 [<a href="/pmc/articles/PMC4469305/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4469305</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25135635" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25135635</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>120.</dt><dd><div class="bk_ref" id="ch5.ref120">Kim
|
|
JH, Kim
|
|
JM, Cho
|
|
YZ, Na
|
|
JH, Kim
|
|
HS, Kim
|
|
HA
|
|
et al. Effects of candesartan and propranolol combination therapy versus propranolol monotherapy in reducing portal hypertension. Clinical and molecular hepatology. 2014; 20(4):376–383 [<a href="/pmc/articles/PMC4278069/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4278069</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25548744" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25548744</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>121.</dt><dd><div class="bk_ref" id="ch5.ref121">Kim
|
|
KI, Shin
|
|
MS, Ihm
|
|
SH, Youn
|
|
HJ, Sung
|
|
KC, Chae
|
|
SC
|
|
et al. A randomized, double-blind, multicenter, phase III study to evaluate the efficacy and safety of fimasartan/amlodipine combined therapy versus fimasartan monotherapy in patients with essential hypertension unresponsive to fimasartan monotherapy. Clinical Therapeutics. 2016; 38(10):2159–2170 [<a href="https://pubmed.ncbi.nlm.nih.gov/27502326" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27502326</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>122.</dt><dd><div class="bk_ref" id="ch5.ref122">Kim
|
|
SH, Ryu
|
|
KH, Lee
|
|
NH, Kang
|
|
JH, Kim
|
|
WS, Park
|
|
SW
|
|
et al. Efficacy of fixed-dose amlodipine and losartan combination compared with amlodipine monotherapy in stage 2 hypertension: A randomized, double blind, multicenter study. BMC Research Notes. 2011; 4:461 [<a href="/pmc/articles/PMC3219858/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3219858</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22035131" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22035131</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>123.</dt><dd><div class="bk_ref" id="ch5.ref123">Kinouchi
|
|
K, Ichihara
|
|
A, Bokuda
|
|
K, Kurosawa
|
|
H, Itoh
|
|
H. Differential effects in cardiovascular markers between high-dose angiotensin II receptor blocker monotherapy and combination therapy of arb with calcium channel blocker in hypertension (DEAR Trial). International Journal of Hypertension. 2011; 2011:284823 [<a href="/pmc/articles/PMC3132603/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3132603</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21755034" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21755034</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>124.</dt><dd><div class="bk_ref" id="ch5.ref124">Kjeldsen
|
|
SE, Cha
|
|
G, Villa
|
|
G, Mancia
|
|
G, Investigators
|
|
D. Nifedipine GITS/candesartan combination therapy lowers blood pressure across different baseline systolic and diastolic blood pressure categories: DISTINCT study subanalyses. Journal of Clinical Pharmacology. 2016; 56(9):1120–9 [<a href="/pmc/articles/PMC5111757/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5111757</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26829251" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26829251</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>125.</dt><dd><div class="bk_ref" id="ch5.ref125">Kjeldsen
|
|
SE, Hedner
|
|
T, Syvertsen
|
|
JO, Lund-Johansen
|
|
P, Hansson
|
|
L, Lanke
|
|
J
|
|
et al. Influence of age, sex and blood pressure on the principal endpoints of the Nordic Diltiazem (NORDIL) Study. Journal of Hypertension. 2002; 20(6):1231–7 [<a href="https://pubmed.ncbi.nlm.nih.gov/12023696" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12023696</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>126.</dt><dd><div class="bk_ref" id="ch5.ref126">Kjeldsen
|
|
SE, Jamerson
|
|
KA, Bakris
|
|
GL, Pitt
|
|
B, Dahlof
|
|
B, Velazquez
|
|
EJ
|
|
et al. Predictors of blood pressure response to intensified and fixed combination treatment of hypertension: The ACCOMPLISH study. Blood Pressure. 2008; 17(1):7–17 [<a href="https://pubmed.ncbi.nlm.nih.gov/18568687" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18568687</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>127.</dt><dd><div class="bk_ref" id="ch5.ref127">Kostis
|
|
JB, Davis
|
|
BR, Cutler
|
|
J, Grimm
|
|
RH, Jr., Berge
|
|
KG, Cohen
|
|
JD
|
|
et al. Prevention of heart failure by antihypertensive drug treatment in older persons with isolated systolic hypertension. SHEP Cooperative Research Group. JAMA. 1997; 278(3):212–6 [<a href="https://pubmed.ncbi.nlm.nih.gov/9218667" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9218667</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>128.</dt><dd><div class="bk_ref" id="ch5.ref128">Kostis
|
|
JB, Silfani
|
|
T. The combination of olmesartan medoxomil plus hydrochlorothiazide in subjects with stage 2 hypertension: Results of a randomized, double-blind, factorial-design study. American Journal of Hypertension. 2004; 17(5):114A</div></dd></dl><dl class="bkr_refwrap"><dt>129.</dt><dd><div class="bk_ref" id="ch5.ref129">Kuschnir
|
|
E, Bendersky
|
|
M, Resk
|
|
J, Panart
|
|
MS, Guzman
|
|
L, Plotquin
|
|
Y
|
|
et al. Effects of the combination of low-dose nifedipine GITS 20 mg and losartan 50 mg in patients with mild to moderate hypertension. Journal of Cardiovascular Pharmacology. 2004; 43(2):300–5 [<a href="https://pubmed.ncbi.nlm.nih.gov/14716221" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14716221</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>130.</dt><dd><div class="bk_ref" id="ch5.ref130">Lassila
|
|
HC, Sutton-Tyrrell
|
|
K, Schwartz
|
|
F, Wildman
|
|
RP, Kuller
|
|
LH. Antihypertensive medication use 5 years following the systolic hypertension in the elderly program. CVD Prevention. 2000; 3(3):229–234</div></dd></dl><dl class="bkr_refwrap"><dt>131.</dt><dd><div class="bk_ref" id="ch5.ref131">Laurent
|
|
S. Clinical benefit of very-low-dose perindopril-indapamide combination in hypertension. Journal of Hypertension Supplement. 2001; 19(4):S9–14 [<a href="https://pubmed.ncbi.nlm.nih.gov/11848262" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11848262</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>132.</dt><dd><div class="bk_ref" id="ch5.ref132">Li
|
|
EC, Heran
|
|
BS, Wright
|
|
JM. Angiotensin converting enzyme (ACE) inhibitors versus angiotensin receptor blockers for primary hypertension. Cochrane Database of Systematic Reviews
|
|
2014, Issue 8. Art. No.: CD009096. DOI: 10.1002/14651858.CD009096.pub2. [<a href="/pmc/articles/PMC6486121/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6486121</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25148386" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25148386</span></a>] [<a href="http://dx.crossref.org/10.1002/14651858.CD009096.pub2" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">CrossRef</a>]</div></dd></dl><dl class="bkr_refwrap"><dt>133.</dt><dd><div class="bk_ref" id="ch5.ref133">London
|
|
GM, Asmar
|
|
RG, O’Rourke
|
|
MF, Safar
|
|
ME, Reason Project Investigators. Mechanism(s) of selective systolic blood pressure reduction after a low-dose combination of perindopril/indapamide in hypertensive subjects: Comparison with atenolol. Journal of the American College of Cardiology. 2004; 43(1):92–9 [<a href="https://pubmed.ncbi.nlm.nih.gov/14715189" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14715189</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>134.</dt><dd><div class="bk_ref" id="ch5.ref134">Lucas
|
|
CP, Morledge
|
|
JH, Tessman
|
|
DK. Comparison of hydrochlorothiazide and hydrochlorothiazide plus bevantolol in hypertension. Clinical Therapeutics. 1985; 8(1):49–60 [<a href="https://pubmed.ncbi.nlm.nih.gov/2870810" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2870810</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>135.</dt><dd><div class="bk_ref" id="ch5.ref135">Lv
|
|
J, Zhang
|
|
H, Chen
|
|
Y, Li
|
|
G, Jiang
|
|
L, Singh
|
|
AK
|
|
et al. Combination therapy of prednisone and ACE inhibitor versus ACE-inhibitor therapy alone in patients with IgA nephropathy: A randomized controlled trial. American Journal of Kidney Diseases. 2009; 53(1):26–32 [<a href="https://pubmed.ncbi.nlm.nih.gov/18930568" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18930568</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>136.</dt><dd><div class="bk_ref" id="ch5.ref136">MacDonald
|
|
TM, Williams
|
|
B, Caulfield
|
|
M, Cruickshank
|
|
JK, McInnes
|
|
G, Sever
|
|
P
|
|
et al. Monotherapy versus dual therapy for the initial treatment of hypertension (PATHWAY-1): A randomised double-blind controlled trial. BMJ Open. 2015; 5(8):e007645 [<a href="/pmc/articles/PMC4539389/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4539389</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26253566" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26253566</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>137.</dt><dd><div class="bk_ref" id="ch5.ref137">MacKay
|
|
JH, Arcuri
|
|
KE, Goldberg
|
|
AI, Snapinn
|
|
SM, Sweet
|
|
CS. Losartan and low-dose hydrochlorothiazide in patients with essential hypertension. A double-blind, placebo-controlled trial of concomitant administration compared with individual components. Archives of Internal Medicine. 1996; 156(3):278–85 [<a href="https://pubmed.ncbi.nlm.nih.gov/8572837" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8572837</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>138.</dt><dd><div class="bk_ref" id="ch5.ref138">Malacco
|
|
E, Omboni
|
|
S, Study Group. Antihypertensive effect of zofenopril plus hydrochlorothiazide versus zofenopril monotherapy in patients with essential hypertension according to their cardiovascular risk level: A post hoc analysis. Current Therapeutic Research, Clinical and Experimental. 2008; 69(3):232–42 [<a href="/pmc/articles/PMC3969924/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3969924</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24692801" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24692801</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>139.</dt><dd><div class="bk_ref" id="ch5.ref139">Mallion
|
|
JM, Chamontin
|
|
B, Asmar
|
|
R, De Leeuw
|
|
PW, O’Brien
|
|
E, Duprez
|
|
D
|
|
et al. Twenty-four-hour ambulatory blood pressure monitoring efficacy of perindopril/indapamide first-line combination in hypertensive patients: The REASON study. American Journal of Hypertension. 2004; 17(3):245–51 [<a href="https://pubmed.ncbi.nlm.nih.gov/15001199" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15001199</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>140.</dt><dd><div class="bk_ref" id="ch5.ref140">Mancia
|
|
G, Cha
|
|
G, Gil-Extremera
|
|
B, Harvey
|
|
P, Lewin
|
|
AJ, Villa
|
|
G
|
|
et al. Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: Subgroup analysis of the DISTINCT randomised trial. Journal of Human Hypertension. 2017; 31(3):178–188 [<a href="/pmc/articles/PMC5301082/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5301082</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27511476" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27511476</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>141.</dt><dd><div class="bk_ref" id="ch5.ref141">Mancia
|
|
G, Parati
|
|
G, Bilo
|
|
G, Gao
|
|
P, Fagard
|
|
R, Redon
|
|
J
|
|
et al. Ambulatory blood pressure values in the ongoing telmisartan alone and in combination with ramipril global endpoint trial (ONTARGET). Hypertension. 2012; 60(6):1400–6 [<a href="https://pubmed.ncbi.nlm.nih.gov/23071122" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23071122</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>142.</dt><dd><div class="bk_ref" id="ch5.ref142">Marques da Silva
|
|
P, Haag
|
|
U, Guest
|
|
JF, Brazier
|
|
JE, Soro
|
|
M. Health-related quality of life impact of a triple combination of olmesartan medoxomil, amlodipine besylate and hydrochlorotiazide in subjects with hypertension. Health & Quality of Life Outcomes. 2015; 13(24):1–13 [<a href="/pmc/articles/PMC4339651/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4339651</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25879524" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25879524</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>143.</dt><dd><div class="bk_ref" id="ch5.ref143">Masao
|
|
I, Kaoru
|
|
Y, Toshikazu
|
|
Y, Tomohiro
|
|
K, Yoshihiro
|
|
K, Michitoshi
|
|
I. Clinical study on long-term drug treatment of mild essential hypertension. Multicenter double-blind trial by group comparison of carteorol and hydrochlorothiazide. Rinsho hyoka. 1994; 22(1):61–104</div></dd></dl><dl class="bkr_refwrap"><dt>144.</dt><dd><div class="bk_ref" id="ch5.ref144">Matsuzaki
|
|
M, Ogihara
|
|
T, Umemoto
|
|
S, Rakugi
|
|
H, Matsuoka
|
|
H, Shimada
|
|
K
|
|
et al. Prevention of cardiovascular events with calcium channel blocker-based combination therapies in patients with hypertension: A randomized controlled trial. Journal of Hypertension. 2011; 29(8):1649–59 [<a href="https://pubmed.ncbi.nlm.nih.gov/21610513" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21610513</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>145.</dt><dd><div class="bk_ref" id="ch5.ref145">Mayaudon
|
|
H, Chanudet
|
|
X, Janin
|
|
G, Madonna
|
|
O. Comparison of the efficacy of enalapril + hydrochlorothiazide and captopril + hydrochlorothiazide combinations on mild-to-moderate hypertension by ambulant blood pressure monitoring. Annales de Cardiologie et d’Angeiologie. 1995; 44(5):235–241 [<a href="https://pubmed.ncbi.nlm.nih.gov/7639505" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7639505</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>146.</dt><dd><div class="bk_ref" id="ch5.ref146">Mazza
|
|
A, Sacco
|
|
AP, Townsend
|
|
DM, Bregola
|
|
G, Contatto
|
|
E, Cappello
|
|
I
|
|
et al. Cost-benefit effectiveness of angiotensin-II receptor blockers in patients with uncomplicated hypertension: A comparative analysis. Biomedicine and Pharmacotherapy. 2017; 90:665–669 [<a href="/pmc/articles/PMC5553545/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5553545</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28415046" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28415046</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>147.</dt><dd><div class="bk_ref" id="ch5.ref147">Miyoshi
|
|
T, Murakami
|
|
T, Sakuragi
|
|
S, Doi
|
|
M, Nanba
|
|
S, Mima
|
|
A
|
|
et al. Comparable effect of aliskiren or a diuretic added on an angiotensin II receptor blocker on augmentation index in hypertension: A multicentre, prospective, randomised study. Open Heart. 2017; 4(1):e000591 [<a href="/pmc/articles/PMC5384463/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5384463</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28409014" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28409014</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>148.</dt><dd><div class="bk_ref" id="ch5.ref148">Mogensen
|
|
CE, Viberti
|
|
G, Halimi
|
|
S, Ritz
|
|
E, Ruilope
|
|
L, Jermendy
|
|
G
|
|
et al. Effect of low-dose perindopril/indapamide on albuminuria in diabetes - Preterax in albuminuria regression: Premier. Hypertension. 2003; 41(5):1063–1071 [<a href="https://pubmed.ncbi.nlm.nih.gov/12654706" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12654706</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>149.</dt><dd><div class="bk_ref" id="ch5.ref149">Morgan
|
|
T, Anderson
|
|
A. A comparison of candesartan, felodipine, and their combination in the treatment of elderly patients with systolic hypertension. American Journal of Hypertension. 2002; 15(6):544–9 [<a href="https://pubmed.ncbi.nlm.nih.gov/12074357" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12074357</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>150.</dt><dd><div class="bk_ref" id="ch5.ref150">Morgan
|
|
T, Anderson
|
|
A, Bertram
|
|
D, MacInnis
|
|
RJ. Effect of candesartan and lisinopril alone and in combination on blood pressure and microalbuminuria. Journal of the Renin-Angiotensin-Aldosterone System. 2004; 5(2):64–71 [<a href="https://pubmed.ncbi.nlm.nih.gov/15295717" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15295717</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>151.</dt><dd><div class="bk_ref" id="ch5.ref151">MRC Working Party. Medical Research Council trial of treatment of hypertension in older adults: Principal results. MRC Working Party. BMJ. 1992; 304(6824):405–12 [<a href="/pmc/articles/PMC1995577/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1995577</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/1445513" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1445513</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>152.</dt><dd><div class="bk_ref" id="ch5.ref152">Nakao
|
|
N, Seno
|
|
H, Kasuga
|
|
H, Toriyama
|
|
T, Kawahara
|
|
H, Fukagawa
|
|
M. Effects of combination treatment with losartan and trandolapril on office and ambulatory blood pressures in non-diabetic renal disease: A COOPERATE-ABP substudy. American Journal of Nephrology. 2004; 24(5):543–548 [<a href="https://pubmed.ncbi.nlm.nih.gov/15528874" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15528874</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>153.</dt><dd><div class="bk_ref" id="ch5.ref153">Nalbantgil
|
|
S, Zoghi
|
|
M, Ozerkan
|
|
F, Boydak
|
|
B, Nalbantgil
|
|
I, Onder
|
|
R
|
|
et al. Comparison of candesartan and felodipine alone and combined in the treatment of hypertension: A single-center, double-blind, randomized, crossover trial. Current Therapeutic Research, Clinical and Experimental. 2003; 64(7):380–8 [<a href="/pmc/articles/PMC4053044/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4053044</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24944389" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24944389</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>154.</dt><dd><div class="bk_ref" id="ch5.ref154">National Clinical Guideline Centre. Hypertension: the clinical managment of primary hypertension in adults: update of clinical guidelines 18 and 34. NICE clinical guideline 127. London. National Clinical Guideline Centre, 2011. Available from: <a href="http://guidance.nice.org.uk/CG127" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">http://guidance<wbr style="display:inline-block"></wbr>​.nice.org.uk/CG127</a></div></dd></dl><dl class="bkr_refwrap"><dt>155.</dt><dd><div class="bk_ref" id="ch5.ref155">National Institute for Health and Care Excellence. Developing NICE guidelines: the manual. London. National Institute for Health and Care Excellence, 2014. Available from: <a href="http://www.nice.org.uk/article/PMG20/chapter/1%20Introduction%20and%20overview" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">http://www<wbr style="display:inline-block"></wbr>​.nice.org.uk<wbr style="display:inline-block"></wbr>​/article/PMG20/chapter<wbr style="display:inline-block"></wbr>​/1%20Introduction%20and%20overview</a> [<a href="https://pubmed.ncbi.nlm.nih.gov/26677490" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26677490</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>156.</dt><dd><div class="bk_ref" id="ch5.ref156">Nedogoda
|
|
SV, Marchenko
|
|
IV, Chaliabi
|
|
TA, Tsoma
|
|
VV, Brel
|
|
UA, Prokhorova
|
|
EA. Comparative efficacy of fixed dose combinations of perindopril with indapamide and captopril with hydrochlorothiazide in patients with high risk hypertension. Kardiologiia. 2005; 45(11):24–26 [<a href="https://pubmed.ncbi.nlm.nih.gov/16353060" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16353060</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>157.</dt><dd><div class="bk_ref" id="ch5.ref157">Neldam
|
|
S, Edwards
|
|
C, Lang
|
|
M, Jones
|
|
R, Teamsta
|
|
Investigators. Long-term tolerability and efficacy of single-pill combinations of telmisartan 40–80 mg Plus amlodipine 5 or 10 mg in patients whose blood pressure was not initially controlled by amlodipine 5–10 mg: Open-label, long-term follow-ups of the TEAMSTA-5 and TEAMSTA-10 studies. Current Therapeutic Research, Clinical and Experimental. 2012; 73(1–2):65–84 [<a href="/pmc/articles/PMC3954024/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3954024</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24653513" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24653513</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>158.</dt><dd><div class="bk_ref" id="ch5.ref158">Neldam
|
|
S, Schumacher
|
|
H, Guthrie
|
|
R. Telmisartan 80 mg/hydrochlorothiazide 25 mg provides clinically relevant blood pressure reductions across baseline blood pressures. Advances in Therapy. 2012; 29(4):327–38 [<a href="https://pubmed.ncbi.nlm.nih.gov/22477543" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22477543</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>159.</dt><dd><div class="bk_ref" id="ch5.ref159">Nelson
|
|
GI, Donnelly
|
|
GL, Hunyor
|
|
SN. Haemodynamic effects of sustained treatment with prazosin and metoprolol, alone and in combination, in borderline hypertensive heart failure. Journal of Cardiovascular Pharmacology. 1982; 4(2):240–245 [<a href="https://pubmed.ncbi.nlm.nih.gov/6175807" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6175807</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>160.</dt><dd><div class="bk_ref" id="ch5.ref160">Neutel
|
|
JM, Giles
|
|
TD, Punzi
|
|
H, Weiss
|
|
RJ, Li
|
|
H, Finck
|
|
A. Long-term safety of nebivolol and valsartan combination therapy in patients with hypertension: An open-label, single-arm, multicenter study. Journal of the American Society of Hypertension. 2014; 8(12):915–20 [<a href="https://pubmed.ncbi.nlm.nih.gov/25492835" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25492835</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>161.</dt><dd><div class="bk_ref" id="ch5.ref161">Neutel
|
|
JM, Smith
|
|
DH, Weber
|
|
MA. Low dose combination therapy vs. high dose monotherapy in the management of hypertension. Journal of Clinical Hypertension. 1999; 1(3):79–86 [<a href="https://pubmed.ncbi.nlm.nih.gov/11416610" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11416610</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>162.</dt><dd><div class="bk_ref" id="ch5.ref162">Neutel
|
|
JM, Weir
|
|
MR, Moser
|
|
M, Harris
|
|
S, Edwards
|
|
D, Michelson
|
|
EL
|
|
et al. The effects of candesartan cilexetil in isolated systolic hypertension: A clinical experience trial. Journal of Clinical Hypertension. 2000; 2(3):181–186 [<a href="https://pubmed.ncbi.nlm.nih.gov/11416644" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11416644</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>163.</dt><dd><div class="bk_ref" id="ch5.ref163">Obel
|
|
AO. Efficacy and tolerability of long term oxprenolol and chlortalidone singly and in combination in hypertensive blacks. Japanese Heart Journal. 1990; 31(2):183–92 [<a href="https://pubmed.ncbi.nlm.nih.gov/2192098" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2192098</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>164.</dt><dd><div class="bk_ref" id="ch5.ref164">Oliván Martínez
|
|
J, Hoyos Jiménez
|
|
M, Miranda García
|
|
MJ, Justo Alpañés
|
|
E, Pérez Cano
|
|
R. Double blind comparative randomized study of the efficacy of celiprolol versus amiloride-hydrochlorothiazide in mild to moderate AHT. Anales de Medicina Interna. 1993; 10(5):221–227 [<a href="https://pubmed.ncbi.nlm.nih.gov/8518337" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8518337</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>165.</dt><dd><div class="bk_ref" id="ch5.ref165">Packer
|
|
M, Carson
|
|
P, Elkayam
|
|
U, Konstam
|
|
MA, Moe
|
|
G, O’Connor
|
|
C
|
|
et al. Effect of amlodipine on the survival of patients with severe chronic heart failure due to a nonischemic cardiomyopathy: Results of the PRAISE-2 study (prospective randomized amlodipine survival evaluation 2). JACC Heart failure. 2013; 1(4):308–314 [<a href="https://pubmed.ncbi.nlm.nih.gov/24621933" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24621933</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>166.</dt><dd><div class="bk_ref" id="ch5.ref166">Pannier
|
|
B, Guerin
|
|
A, London
|
|
G, Asmar
|
|
R, Safar
|
|
M. Combination of low dose perindopril/indapamide versus atenolol in the hypertensive patient: Effects on systolic blood pressure and arterial haemodynamics. Archives des Maladies du Coeur et des Vaisseaux. 2002; 95(Special 6):11–16 [<a href="https://pubmed.ncbi.nlm.nih.gov/12407781" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12407781</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>167.</dt><dd><div class="bk_ref" id="ch5.ref167">Papademetriou
|
|
V. Comparison of Nebivolol monotherapy versus Nebivolol in combination with other antihypertensive therapies for the treatment of hypertension. American Journal of Cardiology. 2009; 103(2):273–8 [<a href="https://pubmed.ncbi.nlm.nih.gov/19121451" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19121451</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>168.</dt><dd><div class="bk_ref" id="ch5.ref168">Papademetriou
|
|
V, Prisant
|
|
LM, Neutel
|
|
JM, Weir
|
|
MR. Efficacy of low-dose combination of bisoprolol/hydrochlorothiazide compared with amlodipine and enalapril in men and women with essential hypertension. American Journal of Cardiology. 1998; 81(11):1363–5 [<a href="https://pubmed.ncbi.nlm.nih.gov/9631978" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9631978</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>169.</dt><dd><div class="bk_ref" id="ch5.ref169">Park
|
|
CG, Ahn
|
|
TH, Cho
|
|
EJ, Kim
|
|
W, Kim
|
|
HS, Yang
|
|
JY
|
|
et al. Comparison of the efficacy and safety of fixed-dose s-amlodipine/telmisartan and telmisartan in hypertensive patients inadequately controlled with telmisartan: A randomized, double-blind, multicenter study. Clinical Therapeutics. 2016; 38(10):2185–2194 [<a href="https://pubmed.ncbi.nlm.nih.gov/27720505" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27720505</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>170.</dt><dd><div class="bk_ref" id="ch5.ref170">Park
|
|
JB, Shin
|
|
JH, Kim
|
|
DS, Youn
|
|
HJ, Park
|
|
SW, Shim
|
|
WJ
|
|
et al. Safety of the up-titration of nifedipine GITS and valsartan or low-dose combination in uncontrolled hypertension: The FOCUS Study. Clinical Therapeutics. 2016; 38(4):832–42 [<a href="https://pubmed.ncbi.nlm.nih.gov/26996246" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26996246</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>171.</dt><dd><div class="bk_ref" id="ch5.ref171">Park
|
|
JS, Shin
|
|
JH, Hong
|
|
TJ, Seo
|
|
HS, Shim
|
|
WJ, Baek
|
|
SH
|
|
et al. Efficacy and safety of fixed-dose combination therapy with olmesartan medoxomil and rosuvastatin in Korean patients with mild to moderate hypertension and dyslipidemia: An 8-week, multicenter, randomized, double-blind, factorial-design study (OLSTA-D RCT: OLmesartan rosuvaSTAtin from Daewoong). Drug Design, Development and Therapy. 2016; 10:2599–609 [<a href="/pmc/articles/PMC4993275/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4993275</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27574399" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27574399</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>172.</dt><dd><div class="bk_ref" id="ch5.ref172">Patel
|
|
A, Advance Collaborative Group, MacMahon
|
|
S, Chalmers
|
|
J, Neal
|
|
B, Woodward
|
|
M
|
|
et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): A randomised controlled trial. The Lancet. 2007; 370(9590):829–40 [<a href="https://pubmed.ncbi.nlm.nih.gov/17765963" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17765963</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>173.</dt><dd><div class="bk_ref" id="ch5.ref173">Paz
|
|
MA, de-La-Sierra
|
|
A, Saez
|
|
M, Barcelo
|
|
MA, Rodriguez
|
|
JJ, Castro
|
|
S
|
|
et al. Treatment efficacy of anti-hypertensive drugs in monotherapy or combination: ATOM systematic review and meta-analysis of randomized clinical trials according to PRISMA statement. Medicine. 2016; 95(30):e4071 [<a href="/pmc/articles/PMC5265817/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5265817</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27472680" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27472680</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>174.</dt><dd><div class="bk_ref" id="ch5.ref174">Perez-Maraver
|
|
M, Carrera
|
|
MJ, Micalo
|
|
T, Sahun
|
|
M, Vinzia
|
|
C, Soler
|
|
J
|
|
et al. Renoprotective effect of diltiazem in hypertensive type 2 diabetic patients with persistent microalbuminuria despite ACE inhibitor treatment. Diabetes Research and Clinical Practice. 2005; 70(1):13–9 [<a href="https://pubmed.ncbi.nlm.nih.gov/16126118" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16126118</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>175.</dt><dd><div class="bk_ref" id="ch5.ref175">Persson
|
|
I. Combination therapy of essential hypertension with pindolol (Visken) and hydralazine. Advances in Clinical Pharmacology. 1976; 11:1114–8 [<a href="https://pubmed.ncbi.nlm.nih.gov/802071" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 802071</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>176.</dt><dd><div class="bk_ref" id="ch5.ref176">Pessina
|
|
AC, Ciccariello
|
|
L, Perrone
|
|
F, Stoico
|
|
V, Gussoni
|
|
G, Scotti
|
|
A
|
|
et al. Clinical efficacy and tolerability of alpha-blocker doxazosin as add-on therapy in patients with hypertension and impaired glucose metabolism. Nutrition, Metabolism, and Cardiovascular Diseases. 2006; 16(2):137–47 [<a href="https://pubmed.ncbi.nlm.nih.gov/16487914" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16487914</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>177.</dt><dd><div class="bk_ref" id="ch5.ref177">Petelina
|
|
TI, Gapon
|
|
LI, Bakhmatova Iu
|
|
A, Zhevagina
|
|
IA. Clinical efficacy of combined therapy with enalapril + trimetazidine in patients with hypertension comorbid with ischemic heart disease and metabolic disturbances. Terapevticheskii Arkhiv. 2005; 77(8):19–23 [<a href="https://pubmed.ncbi.nlm.nih.gov/16206600" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16206600</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>178.</dt><dd><div class="bk_ref" id="ch5.ref178">Petersen
|
|
LJ, Petersen
|
|
JR, Talleruphuus
|
|
U, Moller
|
|
ML, Ladefoged
|
|
SD, Mehlsen
|
|
J
|
|
et al. A randomized and double-blind comparison of isradipine and spirapril as monotherapy and in combination on the decline in renal function in patients with chronic renal failure and hypertension. Clinical Nephrology. 2001; 55(5):375–83 [<a href="https://pubmed.ncbi.nlm.nih.gov/11393383" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11393383</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>179.</dt><dd><div class="bk_ref" id="ch5.ref179">Petrie
|
|
JC, Galloway
|
|
DB, Webster
|
|
J, Simpson
|
|
WT, Lewis
|
|
JA. Atenolol and bendrofluazide in hypertension. British Medical Journal. 1975; 4(5989):133–5 [<a href="/pmc/articles/PMC1674832/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1674832</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/1104047" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1104047</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>180.</dt><dd><div class="bk_ref" id="ch5.ref180">Pool
|
|
JL, Glazer
|
|
R, Crikelair
|
|
N, Levy
|
|
D. The role of baseline blood pressure in guiding treatment choice: A secondary analysis of the use of valsartan/hydrochlorothiazide as initial therapy in hypertensive adults in a randomized, double-blind, placebo-controlled trial. Clinical Drug Investigation. 2009; 29(12):791–802 [<a href="https://pubmed.ncbi.nlm.nih.gov/19888785" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19888785</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>181.</dt><dd><div class="bk_ref" id="ch5.ref181">Prisant
|
|
LM, Neutel
|
|
JM, Papademetriou
|
|
V, DeQuattro
|
|
V, Hall
|
|
WD, Weir
|
|
MR. Low-dose combination treatment for hypertension versus single-drug treatment-bisoprolol/hydrochlorothiazide versus amlodipine, enalapril, and placebo: Combined analysis of comparative studies. American Journal of Therapeutics. 1998; 5(5):313–21 [<a href="https://pubmed.ncbi.nlm.nih.gov/10099075" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10099075</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>182.</dt><dd><div class="bk_ref" id="ch5.ref182">Radevski
|
|
IV, Valtchanova
|
|
SP, Candy
|
|
GP, Tshele
|
|
EF, Sareli
|
|
P. Comparison of acebutolol with and without hydrochlorothiazide versus carvedilol with and without hydrochlorothiazide in black patients with mild to moderate systemic hypertension. American Journal of Cardiology. 1999; 84(1):70–5 [<a href="https://pubmed.ncbi.nlm.nih.gov/10404854" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10404854</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>183.</dt><dd><div class="bk_ref" id="ch5.ref183">Radevski
|
|
IV, Valtchanova
|
|
ZP, Candy
|
|
GP, Hlatswayo
|
|
MN, Sareli
|
|
P. Antihypertensive effect of low-dose hydrochlorothiazide alone or in combination with quinapril in black patients with mild to moderate hypertension. Journal of Clinical Pharmacology. 2000; 40(7):713–21 [<a href="https://pubmed.ncbi.nlm.nih.gov/10883412" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10883412</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>184.</dt><dd><div class="bk_ref" id="ch5.ref184">Rakesh
|
|
O, Pranesh
|
|
K, Bhavin
|
|
V. A randomized active controlled clinical study to evaluate efficacy and safety of resveratrol as an adjuvant therapy in patients with hypertension. Asian Journal of Pharmaceutical and Clinical Research. 2017; 10(1):376–379</div></dd></dl><dl class="bkr_refwrap"><dt>185.</dt><dd><div class="bk_ref" id="ch5.ref185">Ratnasabapathy
|
|
Y, Lawes
|
|
CM, Anderson
|
|
CS. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS): Clinical implications for older patients with cerebrovascular disease. Drugs and Aging. 2003; 20(4):241–51 [<a href="https://pubmed.ncbi.nlm.nih.gov/12641480" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12641480</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>186.</dt><dd><div class="bk_ref" id="ch5.ref186">Redon
|
|
J, Mancia
|
|
G, Sleight
|
|
P, Schumacher
|
|
H, Gao
|
|
P, Pogue
|
|
J
|
|
et al. Safety and efficacy of low blood pressures among patients with diabetes: Subgroup analyses from the ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial). Journal of the American College of Cardiology. 2012; 59(1):74–83 [<a href="https://pubmed.ncbi.nlm.nih.gov/22192672" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22192672</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>187.</dt><dd><div class="bk_ref" id="ch5.ref187">Roca-Cusachs
|
|
A, Torres
|
|
F, Horas
|
|
M, Rios
|
|
J, Calvo
|
|
G, Delgadillo
|
|
J
|
|
et al. Nitrendipine and enalapril combination therapy in mild to moderate hypertension: Assessment of dose-response relationship by a clinical trial of factorial design. Journal of Cardiovascular Pharmacology. 2001; 38(6):840–9 [<a href="https://pubmed.ncbi.nlm.nih.gov/11707687" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11707687</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>188.</dt><dd><div class="bk_ref" id="ch5.ref188">Rosenfeld
|
|
JB, Zabludowski
|
|
J. The efficacy and tolerability of nifedipine (NIF) and nisoldipine (NIS) both alone and combined with a beta-blocker in patients with essential hypertension: A multicenter, parallel-group study. Journal of Clinical Pharmacology. 1989; 29(11):1013–6 [<a href="https://pubmed.ncbi.nlm.nih.gov/2574728" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2574728</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>189.</dt><dd><div class="bk_ref" id="ch5.ref189">Ruggenenti
|
|
P, Fassi
|
|
A, Ilieva
|
|
A, Iliev
|
|
IP, Chiurchiu
|
|
C, Rubis
|
|
N
|
|
et al. Effects of verapamil added-on trandolapril therapy in hypertensive type 2 diabetes patients with microalbuminuria: The BENEDICT-B randomized trial. Journal of Hypertension. 2011; 29(2):207–216 [<a href="https://pubmed.ncbi.nlm.nih.gov/21243736" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21243736</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>190.</dt><dd><div class="bk_ref" id="ch5.ref190">Ruggenenti
|
|
P, Fassi
|
|
A, Ilieva
|
|
AP, Bruno
|
|
S, Iliev
|
|
IP, Brusegan
|
|
V
|
|
et al. Preventing microalbuminuria in type 2 diabetes. New England Journal of Medicine. 2004; 351(19):1941–51 [<a href="https://pubmed.ncbi.nlm.nih.gov/15516697" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15516697</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>191.</dt><dd><div class="bk_ref" id="ch5.ref191">Ruggenenti
|
|
P, Lauria
|
|
G, Iliev
|
|
IP, Fassi
|
|
A, Ilieva
|
|
AP, Rota
|
|
S
|
|
et al. Effects of manidipine and delapril in hypertensive patients with type 2 diabetes mellitus: The delapril and manidipine for nephroprotection in diabetes (DEMAND) randomized clinical trial. Hypertension. 2011; 58(5):776–83 [<a href="https://pubmed.ncbi.nlm.nih.gov/21931073" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21931073</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>192.</dt><dd><div class="bk_ref" id="ch5.ref192">Saito
|
|
I, Kobayashi
|
|
M, Matsushita
|
|
Y, Mori
|
|
A, Kawasugi
|
|
K, Saruta
|
|
T. Cost-utility analysis of antihypertensive combination therapy in Japan by a Monte Carlo simulation model. Hypertension Research. 2008; 31(7):1373–1383 [<a href="https://pubmed.ncbi.nlm.nih.gov/18957808" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18957808</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>193.</dt><dd><div class="bk_ref" id="ch5.ref193">Saruta
|
|
T, Ogihara
|
|
T, Saito
|
|
I, Rakugi
|
|
H, Shimamoto
|
|
K, Matsuoka
|
|
H
|
|
et al. Comparison of olmesartan combined with a calcium channel blocker or a diuretic in elderly hypertensive patients (COLM Study): Safety and tolerability. Hypertension Research. 2015; 38(2):132–6 [<a href="/pmc/articles/PMC4322201/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4322201</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25253582" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25253582</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>194.</dt><dd><div class="bk_ref" id="ch5.ref194">Sassano
|
|
P, Chatellier
|
|
G, Billaud
|
|
E, Corvol
|
|
P, Menard
|
|
J. Comparison of increase in the enalapril dose and addition of hydrochlorothiazide as second-step treatment of hypertensive patients not controlled by enalapril alone. Journal of Cardiovascular Pharmacology. 1989; 13(2):314–9 [<a href="https://pubmed.ncbi.nlm.nih.gov/2468963" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2468963</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>195.</dt><dd><div class="bk_ref" id="ch5.ref195">Seedat
|
|
YK. Guanfacine alone and in combination therapy in the treatment of moderate and severe hypertension. Chest. 1983; 83:(Suppl 2):403–4 [<a href="https://pubmed.ncbi.nlm.nih.gov/6337031" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6337031</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>196.</dt><dd><div class="bk_ref" id="ch5.ref196">Seedat
|
|
YK, Rawat
|
|
R. An evaluation of the antihypertensive effect of enalapril with hydrochlorothiazide and methyldopa compared to propranolol with hydrochlorothiazide and hydralazine in patients with moderate to severe hypertension. Current Therapeutic Research, Clinical and Experimental. 1984; 35(5):851–859</div></dd></dl><dl class="bkr_refwrap"><dt>197.</dt><dd><div class="bk_ref" id="ch5.ref197">Shaifali
|
|
I, Kapoor
|
|
AK, Singh
|
|
HK, Patial
|
|
RK. A comparative evaluation of Losartan/Hydrochlorothiazide (fixed combination) versus Amlodipine monotherapy in patients with hypertension in Rohilkhand region. Internet Journal of Medical Update. 2014; 9(2):9–16</div></dd></dl><dl class="bkr_refwrap"><dt>198.</dt><dd><div class="bk_ref" id="ch5.ref198">Shi
|
|
R, Liu
|
|
K, Shi
|
|
D, Liu
|
|
Q, Chen
|
|
X. Effects of amlodipine and valsartan on blood pressure variability and pulse wave velocity in hypertensive patients. American Journal of the Medical Sciences. 2017; 353(1):6–11 [<a href="https://pubmed.ncbi.nlm.nih.gov/28104105" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28104105</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>199.</dt><dd><div class="bk_ref" id="ch5.ref199">Shimamoto
|
|
K, Kimoto
|
|
M, Matsuda
|
|
Y, Asano
|
|
K, Kajikawa
|
|
M. Long-term safety and efficacy of high-dose controlled-release nifedipine (80 mg per day) in Japanese patients with essential hypertension. Hypertension Research. 2015; 38(10):695–700 [<a href="/pmc/articles/PMC4598367/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4598367</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25876832" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25876832</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>200.</dt><dd><div class="bk_ref" id="ch5.ref200">Smith
|
|
TR, Philipp
|
|
T, Vaisse
|
|
B, Bakris
|
|
GL, Wernsing
|
|
M, Yen
|
|
J
|
|
et al. Amlodipine and valsartan combined and as monotherapy in stage 2, elderly, and black hypertensive patients: Subgroup analyses of 2 randomized, placebo-controlled studies. Journal of Clinical Hypertension. 2007; 9(5):355–64 [<a href="/pmc/articles/PMC8109965/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8109965</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/17485971" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17485971</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>201.</dt><dd><div class="bk_ref" id="ch5.ref201">Sohn
|
|
IS, Kim
|
|
CJ, Ahn
|
|
T, Youn
|
|
HJ, Jeon
|
|
HK, Ihm
|
|
SH
|
|
et al. Efficacy and tolerability of combination therapy versus monotherapy with candesartan and/or amlodipine for dose finding in essential hypertension: A phase II multicenter, randomized, double-blind clinical trial. Clinical Therapeutics. 2017; 39(8):1628–1638 [<a href="https://pubmed.ncbi.nlm.nih.gov/28734660" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28734660</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>202.</dt><dd><div class="bk_ref" id="ch5.ref202">Soucek
|
|
M, Plachý
|
|
M. The FEVER (Felodipine EVEnt Reduction) trial; a randomised, double-blind, placebo-controlled trial in Chinese hypertensive patients. Vnitrni Lekarstvi. 2007; 53(1):63–70 [<a href="https://pubmed.ncbi.nlm.nih.gov/17472017" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17472017</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>203.</dt><dd><div class="bk_ref" id="ch5.ref203">Sung
|
|
J, Jeong
|
|
JO, Kwon
|
|
SU, Won
|
|
KH, Kim
|
|
BJ, Cho
|
|
BR
|
|
et al. Valsartan 160 mg/Amlodipine 5 mg combination therapy versus Amlodipine 10 mg in hypertensive patients with inadequate response to Amlodipine 5 mg monotherapy. Korean Circulation Journal. 2016; 46(2):222–8 [<a href="/pmc/articles/PMC4805567/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4805567</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27014353" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27014353</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>204.</dt><dd><div class="bk_ref" id="ch5.ref204">Szucs
|
|
TD, Waeber
|
|
B, Tomonaga
|
|
Y. Cost-effectiveness of antihypertensive treatment in patients 80 years of age or older in Switzerland: an analysis of the HYVET study from a Swiss perspective. Journal of Human Hypertension. 2010; 24(2):117–123 [<a href="/pmc/articles/PMC3011095/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3011095</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19536166" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19536166</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>205.</dt><dd><div class="bk_ref" id="ch5.ref205">Thijs
|
|
L, Richart
|
|
T, De Leeuw
|
|
PW, Kuznetsova
|
|
T, Grodzicki
|
|
T, Kawecka-Jaszcz
|
|
K
|
|
et al. Morbidity and mortality on combination versus monotherapy: A posthoc analysis of the Systolic Hypertension in Europe trial. Journal of Hypertension. 2010; 28(4):865–874 [<a href="https://pubmed.ncbi.nlm.nih.gov/20051905" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20051905</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>206.</dt><dd><div class="bk_ref" id="ch5.ref206">Timofeeva
|
|
LA, Alekhin
|
|
MN, Ugriumov
|
|
MO, Chumakova
|
|
OS, Larina
|
|
VN, Sidorenko
|
|
BA. Effect of twelve-month combined therapy with perindopril and indapamide on the level of blood pressure and left ventricular hypertrophy in patients with hypertensive disease. Kardiologiia. 2006; 46(3):30–34 [<a href="https://pubmed.ncbi.nlm.nih.gov/16710252" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16710252</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>207.</dt><dd><div class="bk_ref" id="ch5.ref207">Umemoto
|
|
S, Ogihara
|
|
T, Matsuzaki
|
|
M, Rakugi
|
|
H, Ohashi
|
|
Y, Saruta
|
|
T
|
|
et al. Effects of calcium channel blocker-based combinations on intra-individual blood pressure variability: Post hoc analysis of the COPE trial. Hypertension Research. 2016; 39(1):46–53 [<a href="/pmc/articles/PMC4709460/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4709460</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26490089" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26490089</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>208.</dt><dd><div class="bk_ref" id="ch5.ref208">Umemoto
|
|
S, Ogihara
|
|
T, Matsuzaki
|
|
M, Rakugi
|
|
H, Shimada
|
|
K, Kawana
|
|
M
|
|
et al. Effects of calcium-channel blocker benidipine-based combination therapy on cardiac events-subanalysis of the COPE trial. Circulation Journal. 2017; 82(2):457–463 [<a href="https://pubmed.ncbi.nlm.nih.gov/28867690" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28867690</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>209.</dt><dd><div class="bk_ref" id="ch5.ref209">Uzui
|
|
H, Morishita
|
|
T, Nakano
|
|
A, Amaya
|
|
N, Fukuoka
|
|
Y, Ishida
|
|
K
|
|
et al. Effects of combination therapy with olmesartan and azelnidipine on serum osteoprotegerin in patients with hypertension. Journal of Cardiovascular Pharmacology and Therapeutics. 2014; 19(3):304–9 [<a href="https://pubmed.ncbi.nlm.nih.gov/24288395" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24288395</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>210.</dt><dd><div class="bk_ref" id="ch5.ref210">Wang
|
|
JG, Yukisada
|
|
K, Sibulo
|
|
A, Jr., Hafeez
|
|
K, Jia
|
|
Y, Zhang
|
|
J. Efficacy and safety of sacubitril/valsartan (LCZ696) add-on to amlodipine in Asian patients with systolic hypertension uncontrolled with amlodipine monotherapy. Journal of Hypertension. 2017; 35(4):877–885 [<a href="https://pubmed.ncbi.nlm.nih.gov/28030431" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28030431</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>211.</dt><dd><div class="bk_ref" id="ch5.ref211">Weinberger
|
|
MH. Comparison of captopril and hydrochlorothiazide alone and in combination in mild to moderate essential hypertension. British Journal of Clinical Pharmacology. 1982; 14:(Suppl 2):127S–131S [<a href="/pmc/articles/PMC1427520/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1427520</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/6753893" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6753893</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>212.</dt><dd><div class="bk_ref" id="ch5.ref212">Weir
|
|
MR, Wang
|
|
RY. Use of angiotensin II receptor blockers alone and in combination with other drugs: A large clinical experience trial. Journal of the Renin-Angiotensin-Aldosterone System. 2001; 2:(Suppl 1):S217–S222 [<a href="https://pubmed.ncbi.nlm.nih.gov/28095219" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28095219</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>213.</dt><dd><div class="bk_ref" id="ch5.ref213">White
|
|
WB, Stimpel
|
|
M. Long-term safety and efficacy of moexipril alone and in combination with hydrochlorothiazide in elderly patients with hypertension. Journal of Human Hypertension. 1995; 9(11):879–84 [<a href="https://pubmed.ncbi.nlm.nih.gov/8583466" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8583466</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>214.</dt><dd><div class="bk_ref" id="ch5.ref214">Wilhelmsen
|
|
L, Berglund
|
|
G, Elmfeldt
|
|
D, Fitzsimons
|
|
T, Holzgreve
|
|
H, Hosie
|
|
J
|
|
et al. Beta-blockers versus diuretics in hypertensive men: Main results from the HAPPHY trial. Journal of Hypertension. 1987; 5(5):561–72 [<a href="https://pubmed.ncbi.nlm.nih.gov/2892881" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2892881</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>215.</dt><dd><div class="bk_ref" id="ch5.ref215">Wisloff
|
|
T, Selmer
|
|
RM, Halvorsen
|
|
S, Fretheim
|
|
A, Norheim
|
|
OF, Kristiansen
|
|
IS. Choice of generic antihypertensive drugs for the primary prevention of cardiovascular disease: a cost-effectiveness analysis. BMC Cardiovascular Disorders. 2012; 12:26 [<a href="/pmc/articles/PMC3353849/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3353849</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22475076" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22475076</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>216.</dt><dd><div class="bk_ref" id="ch5.ref216">Yip
|
|
GW, Wang
|
|
M, Wang
|
|
T, Chan
|
|
S, Fung
|
|
JW, Yeung
|
|
L
|
|
et al. The Hong Kong diastolic heart failure study: A randomised controlled trial of diuretics, irbesartan and ramipril on quality of life, exercise capacity, left ventricular global and regional function in heart failure with a normal ejection fraction. Heart. 2008; 94(5):573–80 [<a href="https://pubmed.ncbi.nlm.nih.gov/18208835" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18208835</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>217.</dt><dd><div class="bk_ref" id="ch5.ref217">Yu
|
|
LT, Zhu
|
|
J, Tan
|
|
HQ, Wang
|
|
GG, Teo
|
|
KK, Liu
|
|
LS. Telmisartan, ramipril, or both in high-risk Chinese patients: Analysis of ONTARGET China data. Chinese Medical Journal. 2011; 124(12):1763–8 [<a href="https://pubmed.ncbi.nlm.nih.gov/21740829" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21740829</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>218.</dt><dd><div class="bk_ref" id="ch5.ref218">Yusuf
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S, Lonn
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E, Pais
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P, Bosch
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J, Lopez-Jaramillo
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P, Zhu
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J
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et al. Blood-pressure and cholesterol lowering in persons without cardiovascular disease. New England Journal of Medicine. 2016; 374(21):2032–43 [<a href="https://pubmed.ncbi.nlm.nih.gov/27039945" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27039945</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>219.</dt><dd><div class="bk_ref" id="ch5.ref219">Yusuf
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S, Teo
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KK, Pogue
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J, Dyal
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L, Copland
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I, Schumacher
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H
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et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. New England Journal of Medicine. 2008; 358(15):1547–1559 [<a href="https://pubmed.ncbi.nlm.nih.gov/18378520" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18378520</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>220.</dt><dd><div class="bk_ref" id="ch5.ref220">Zanchetti
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A, Parati
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G, Malacco
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E. Zofenopril plus hydrochlorothiazide: Combination therapy for the treatment of mild to moderate hypertension. Drugs. 2006; 66(8):1107–15 [<a href="https://pubmed.ncbi.nlm.nih.gov/16789795" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16789795</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>221.</dt><dd><div class="bk_ref" id="ch5.ref221">Zhang
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JL, Qin
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YW, Zheng
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X, Qiu
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JL, Zhao
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XX, Zou
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DJ. Combination therapy with angiotensin-converting enzyme inhibitors and indapamide impairs glucose tolerance in Chinese hypertensive patients. Blood Pressure. 2010; 19(2):110–8 [<a href="https://pubmed.ncbi.nlm.nih.gov/20053144" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20053144</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>222.</dt><dd><div class="bk_ref" id="ch5.ref222">Zhu
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D, Bays
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H, Gao
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P, Mattheus
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M, Voelker
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B, Ruilope
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LM. Efficacy and tolerability of a single-pill combination of telmisartan 80 mg and hydrochlorothiazide 25 mg according to age, gender, race, hypertension severity, and previous antihypertensive use: planned analyses of a randomized trial. Integrated Blood Pressure Control. 2013; 6:1–14 [<a href="/pmc/articles/PMC3636767/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3636767</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23637556" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23637556</span></a>]</div></dd></dl></dl></div><div id="appendixesappgroup5"><h2 id="_appendixesappgroup5_">Appendices</h2><div id="ch5.appa"><h3>Appendix A. Review protocols</h3><p id="ch5.appa.tab1"><a href="/books/NBK578061/table/ch5.appa.tab1/?report=objectonly" target="object" rid-ob="figobch5appatab1" class="figpopup">Table 8. Review protocol: Step 1 antihypertensive treatment</a></p><p id="ch5.appa.tab2"><a href="/books/NBK578061/table/ch5.appa.tab2/?report=objectonly" target="object" rid-ob="figobch5appatab2" class="figpopup">Table 9. Health economic review protocol</a></p></div><div id="ch5.appb"><h3>Appendix B. Literature search strategies</h3><p>The literature searches for this review are detailed below and complied with the methodology outlined in <a href="https://www.nice.org.uk/guidance/pmg20/resources/developing-nice-guidelines-the-manual-pdf-72286708700869" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual 2014, updated 2017</a></p><p>For more detailed information, please see the Methodology Review.</p><div id="ch5.appb.s1"><h4>B.1. Clinical search literature search strategy</h4><p>Searches were constructed using a PICO framework where population (P) terms were combined with Intervention (I) and in some cases Comparison (C) terms. Outcomes (O) are rarely used in search strategies for interventions as these concepts may not be well described in title, abstract or indexes and therefore difficult to retrieve. Search filters were applied to the search where appropriate.</p><p id="ch5.appb.tab1"><a href="/books/NBK578061/table/ch5.appb.tab1/?report=objectonly" target="object" rid-ob="figobch5appbtab1" class="figpopup">Table 10. Database date parameters and filters used</a></p><p id="ch5.appb.tab2"><a href="/books/NBK578061/table/ch5.appb.tab2/?report=objectonly" target="object" rid-ob="figobch5appbtab2" class="figpopup">Table 11. Medline (Ovid) search terms</a></p><p id="ch5.appb.tab3"><a href="/books/NBK578061/table/ch5.appb.tab3/?report=objectonly" target="object" rid-ob="figobch5appbtab3" class="figpopup">Table 12. Embase (Ovid) search terms</a></p><p id="ch5.appb.tab4"><a href="/books/NBK578061/table/ch5.appb.tab4/?report=objectonly" target="object" rid-ob="figobch5appbtab4" class="figpopup">Table 13. Cochrane Library (Wiley) search terms</a></p></div><div id="ch5.appb.s2"><h4>B.2. Health Economics literature search strategy</h4><p>Health economic evidence was identified by conducting a broad search relating to hypertension in adults population in NHS Economic Evaluation Database (NHS EED – this ceased to be updated after March 2015) and the Health Technology Assessment database (HTA) with no date restrictions. NHS EED and HTA databases are hosted by the Centre for Research and Dissemination (CRD). Additional searches were run on Medline and Embase for health economics, economic modelling and quality of life studies.</p><p id="ch5.appb.tab5"><a href="/books/NBK578061/table/ch5.appb.tab5/?report=objectonly" target="object" rid-ob="figobch5appbtab5" class="figpopup">Table 14. Database date parameters and filters used</a></p><p id="ch5.appb.tab6"><a href="/books/NBK578061/table/ch5.appb.tab6/?report=objectonly" target="object" rid-ob="figobch5appbtab6" class="figpopup">Table 15. Medline (Ovid) search terms</a></p><p id="ch5.appb.tab7"><a href="/books/NBK578061/table/ch5.appb.tab7/?report=objectonly" target="object" rid-ob="figobch5appbtab7" class="figpopup">Table 16. Embase (Ovid) search terms</a></p><p id="ch5.appb.tab8"><a href="/books/NBK578061/table/ch5.appb.tab8/?report=objectonly" target="object" rid-ob="figobch5appbtab8" class="figpopup">Table 17. NHS EED and HTA (CRD) search terms</a></p></div></div><div id="ch5.appc"><h3>Appendix C. Clinical evidence selection</h3><p id="ch5.appc.fig1"><a href="/books/NBK578061/figure/ch5.appc.fig1/?report=objectonly" target="object" rid-ob="figobch5appcfig1" class="figpopup">Figure 1. Flow chart of clinical study selection for the review of step 1 antihypertensive treatment</a></p></div><div id="ch5.appd"><h3>Appendix D. Clinical evidence tables</h3><p id="ch5.appd.et1"><a href="/books/NBK578061/bin/ch5-appd-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (177K)</span></p></div><div id="ch5.appe"><h3>Appendix E. Forest plots</h3><div id="ch5.appe.s1"><h4>E.1. Combination versus monotherapy in adults with primary hypertension and type 2 diabetes</h4><p id="ch5.appe.fig1"><a href="/books/NBK578061/figure/ch5.appe.fig1/?report=objectonly" target="object" rid-ob="figobch5appefig1" class="figpopup">Figure 2. Serious cardiovascular events at 12 months</a></p><p id="ch5.appe.fig2"><a href="/books/NBK578061/figure/ch5.appe.fig2/?report=objectonly" target="object" rid-ob="figobch5appefig2" class="figpopup">Figure 3. Change in creatinine at 12 months</a></p><p id="ch5.appe.fig3"><a href="/books/NBK578061/figure/ch5.appe.fig3/?report=objectonly" target="object" rid-ob="figobch5appefig3" class="figpopup">Figure 4. Discontinuation due to adverse events at 12 months</a></p><p id="ch5.appe.fig4"><a href="/books/NBK578061/figure/ch5.appe.fig4/?report=objectonly" target="object" rid-ob="figobch5appefig4" class="figpopup">Figure 5. Discontinuation due to adverse events at 12 months (including type 2 diabetes)</a></p><p id="ch5.appe.fig5"><a href="/books/NBK578061/figure/ch5.appe.fig5/?report=objectonly" target="object" rid-ob="figobch5appefig5" class="figpopup">Figure 6. Hypotension (dizziness) at 12 months</a></p></div><div id="ch5.appe.s2"><h4>E.2. Combination versus monotherapy in adults with primary hypertension without type 2 diabetes</h4><p id="ch5.appe.fig6"><a href="/books/NBK578061/figure/ch5.appe.fig6/?report=objectonly" target="object" rid-ob="figobch5appefig6" class="figpopup">Figure 7. Change in creatinine (μmol/L) at 12 months</a></p><p id="ch5.appe.fig7"><a href="/books/NBK578061/figure/ch5.appe.fig7/?report=objectonly" target="object" rid-ob="figobch5appefig7" class="figpopup">Figure 8. Discontinuation due to adverse events at 12 months</a></p></div></div><div id="ch5.appf"><h3>Appendix F. GRADE tables</h3><p id="ch5.appf.tab1"><a href="/books/NBK578061/table/ch5.appf.tab1/?report=objectonly" target="object" rid-ob="figobch5appftab1" class="figpopup">Table 18. Clinical evidence profile: combination versus monotherapy in adults with primary hypertension and type 2 diabetes</a></p><p id="ch5.appf.tab2"><a href="/books/NBK578061/table/ch5.appf.tab2/?report=objectonly" target="object" rid-ob="figobch5appftab2" class="figpopup">Table 19. Clinical evidence profile: combination versus monotherapy in adults with primary hypertension and without type 2 diabetes</a></p></div><div id="ch5.appg"><h3>Appendix G. Health economic evidence selection</h3><p id="ch5.appg.fig1"><a href="/books/NBK578061/figure/ch5.appg.fig1/?report=objectonly" target="object" rid-ob="figobch5appgfig1" class="figpopup">Figure 9. Flow chart of health economic study selection for the guideline</a></p></div><div id="ch5.apph"><h3>Appendix H. Health economic evidence tables</h3><p>None.</p></div><div id="ch5.appi"><h3>Appendix I. Excluded studies</h3><div id="ch5.appi.s1"><h4>I.1. Excluded clinical studies</h4><p id="ch5.appi.tab1"><a href="/books/NBK578061/table/ch5.appi.tab1/?report=objectonly" target="object" rid-ob="figobch5appitab1" class="figpopup">Table 20. Studies excluded from the clinical review</a></p></div><div id="ch5.appi.s2"><h4>I.2. Excluded health economic studies</h4><p id="ch5.appi.tab2"><a href="/books/NBK578061/table/ch5.appi.tab2/?report=objectonly" target="object" rid-ob="figobch5appitab2" class="figpopup">Table 21. Studies excluded from the health economic review</a></p></div></div><div id="ch5.appj"><h3>Appendix J. Research recommendations</h3><div id="ch5.appj.s1"><h4>J.1. Dual therapy</h4><p>
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<b>Research question: Are there subgroups of people with hypertension who should start on dual therapy?</b>
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</p><p>
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<b>Why this is important:</b>
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</p><p>The physiological control of blood pressure results from the interaction of multiple biological pathways, including those acting on the kidneys and blood vessels. Most antihypertensive medication act on a single component of these pathways and so are intrinsically limited in their ability to lower blood pressure. This is the principle reason that many people prescribed antihypertensive medication require more than 1 type of medication to achieve their target blood pressure.</p><p>In the evidence review for step 1 treatment, the committee considered whether individuals with hypertension should be commenced on single or dual therapy. Only limited evidence on cardiovascular events was available from a single study, and this was felt to be insufficient to determine confidently whether dual therapy may be beneficial. The theoretical benefit of starting dual therapy is that more rapid achievement of target blood pressure may lead to a reduction in cardiovascular events. It is unknown whether dual therapy may be of benefit to all individuals commencing antihypertensive medication or just certain subgroups such as those with type 2 diabetes, established cardiovascular disease or chronic kidney disease.</p><p id="ch5.appj.tab1"><a href="/books/NBK578061/table/ch5.appj.tab1/?report=objectonly" target="object" rid-ob="figobch5appjtab1" class="figpopup">Criteria for selecting high-priority research recommendations</a></p></div></div></div></div><div class="fm-sec"><div><p>Final</p></div><div><p>Intervention evidence review underpinning recommendations 1.4.30 to 1.4.37 in the guideline</p><p>This evidence review was developed by the National Guideline Centre</p></div><div><p><b>Disclaimer</b>: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.</p><p>Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.</p><p>NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the <a href="http://wales.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Welsh Government</a>, <a href="http://www.scotland.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Scottish Government</a>, and <a href="http://www.northernireland.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Northern Ireland Executive</a>. All NICE guidance is subject to regular review and may be updated or withdrawn.</p></div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © NICE 2019.</div><div class="small"><span class="label">Bookshelf ID: NBK578061</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/35188723" title="PubMed record of this title" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">35188723</a></span></div></div><div class="small-screen-prev"></div><div class="small-screen-next"></div></article><article data-type="table-wrap" id="figobch5tab1"><div id="ch5.tab1" class="table"><h3><span class="label">Table 1</span><span class="title">PICO characteristics of review question</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.tab1_lrgtbl__"><table><tbody><tr><th id="hd_b_ch5.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><td headers="hd_b_ch5.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Adults (over 18 years) with primary hypertension who are not on current pharmacological treatment for hypertension (minimum wash-out 4 weeks)</td></tr><tr><th id="hd_b_ch5.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</th><td headers="hd_b_ch5.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Combination antihypertensive therapy – adjunct or non-adjunct (definition: 2 antihypertensive medications prescribed simultaneously – may be in 1 pill or 2). Examples include:
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<ul id="ch5.l1"><li id="ch5.lt1" class="half_rhythm"><div>Angiotensin-converting enzyme (ACE) inhibitor and calcium channel blocker (CCB)</div></li><li id="ch5.lt2" class="half_rhythm"><div>Angiotensin-II receptor blocker (ARB) and CCB</div></li><li id="ch5.lt3" class="half_rhythm"><div>ACE inhibitor and diuretic (thiazide like or conventional)</div></li><li id="ch5.lt4" class="half_rhythm"><div>ARB and diuretic (thiazide like or conventional)</div></li><li id="ch5.lt5" class="half_rhythm"><div>ACE inhibitor and CCB (Trandolapril and verapamil; TARKA)</div></li><li id="ch5.lt6" class="half_rhythm"><div>Beta blocker and CCB (atenolol and nifedipine)</div></li><li id="ch5.lt7" class="half_rhythm"><div>Beta blocker and thiazides (atenolol and chlortalidone, chlortalidone; timolol and bendroflumethiazide)</div></li><li id="ch5.lt8" class="half_rhythm"><div>Non-thiazide and thiazide diuretic (amiloride and hydrochlorothiazide)</div></li></ul></td></tr><tr><th id="hd_b_ch5.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparison</th><td headers="hd_b_ch5.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Antihypertensive Monotherapy. Examples include:
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<ul id="ch5.l2"><li id="ch5.lt9" class="half_rhythm"><div>ACE inhibitor or low-cost ARB)</div></li><li id="ch5.lt10" class="half_rhythm"><div>Thiazide-like diuretic (such as chlortalidone chlortalidoneor indapamide)</div></li><li id="ch5.lt11" class="half_rhythm"><div>Conventional thiazide diuretic (such as bendroflumethiazide or hydrochlorothiazide)</div></li><li id="ch5.lt12" class="half_rhythm"><div>CCB</div></li><li id="ch5.lt13" class="half_rhythm"><div>Beta-blockers</div></li><li id="ch5.lt14" class="half_rhythm"><div>Aliskiren (direct renin inhibitors)</div></li><li id="ch5.lt15" class="half_rhythm"><div>Doxazosin, prazosin, terazosin, (alpha blockers)</div></li><li id="ch5.lt16" class="half_rhythm"><div>Clonidine, moxonidine, methyldopa (centrally acting anti-HTN)</div></li></ul></td></tr><tr><th id="hd_b_ch5.tab1_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes</th><td headers="hd_b_ch5.tab1_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Assessed 12 months or more (using final endpoint)</p>
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<p><b>Critical</b>
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<ul id="ch5.l3"><li id="ch5.lt17" class="half_rhythm"><div>All-cause mortality</div></li><li id="ch5.lt18" class="half_rhythm"><div>Health-related quality of life</div></li><li id="ch5.lt19" class="half_rhythm"><div>Stroke (ischaemic or haemorrhagic)</div></li><li id="ch5.lt20" class="half_rhythm"><div>Myocardial infarction (MI)</div></li></ul></p>
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<p><b>Important</b>
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<ul id="ch5.l4"><li id="ch5.lt21" class="half_rhythm"><div>Heart failure needing hospitalisation</div></li><li id="ch5.lt22" class="half_rhythm"><div>Vascular procedures (including both coronary and carotid artery procedures)</div></li><li id="ch5.lt23" class="half_rhythm"><div>Angina needing hospitalisation</div></li><li id="ch5.lt24" class="half_rhythm"><div>Discontinuation or dose reduction due to side effects</div></li><li id="ch5.lt25" class="half_rhythm"><div>Side effect 1: Acute kidney injury</div></li><li id="ch5.lt26" class="half_rhythm"><div>Side effect 2: New onset diabetes</div></li><li id="ch5.lt27" class="half_rhythm"><div>Side effect 3: Changes in eGFR or creatinine</div></li><li id="ch5.lt28" class="half_rhythm"><div>Side effect 4: Hypotension (dizziness)</div></li><li id="ch5.lt29" class="half_rhythm"><div>[Combined cardiovascular disease outcomes in the absence of MI and stroke data]</div></li><li id="ch5.lt30" class="half_rhythm"><div>[Coronary heart disease outcome in the absence of MI data]</div></li></ul></p>
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</td></tr><tr><th id="hd_b_ch5.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study design</th><td headers="hd_b_ch5.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Randomised control trials (RCT) and Systematic reviews (SR)</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5tab2"><div id="ch5.tab2" class="table"><h3><span class="label">Table 2</span><span class="title">Summary of studies included in the evidence review</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.tab2_lrgtbl__"><table><thead><tr><th id="hd_h_ch5.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Study</th><th id="hd_h_ch5.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Intervention and comparison</th><th id="hd_h_ch5.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Population</th><th id="hd_h_ch5.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Outcomes</th><th id="hd_h_ch5.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Comments</th></tr></thead><tbody><tr><td headers="hd_h_ch5.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<b>Asmar 2003 (REASON trial)</b>
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<a class="bibr" href="#ch5.ref14" rid="ch5.ref14">
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<sup>14</sup>
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</a>
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<sup>,</sup>
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<a class="bibr" href="#ch5.ref13" rid="ch5.ref13">
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<sup>13</sup>
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</a>
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<sup>,</sup>
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<a class="bibr" href="#ch5.ref133" rid="ch5.ref133">
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<sup>133</sup>
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</a>
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<sup>,</sup>
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<a class="bibr" href="#ch5.ref139" rid="ch5.ref139">
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<sup>139</sup>
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</a>
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<sup>,</sup>
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<a class="bibr" href="#ch5.ref52" rid="ch5.ref52">
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<sup>52</sup>
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</a>
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</td><td headers="hd_h_ch5.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Combination:</p>
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<p>Perindopril 2 mg plus indapamide 0.625 mg (n=235)</p>
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<p>Monotherapy:</p>
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<p>Atenolol 50 mg (n=234)</p>
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</td><td headers="hd_h_ch5.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hypertension (Systolic BP 160–210; Diastolic BP 95–110 mmHg) without type 2 diabetes (n=471)</td><td headers="hd_h_ch5.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">At 12 months:
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<ul id="ch5.l5"><li id="ch5.lt31" class="half_rhythm"><div>Discontinuation due to adverse events</div></li><li id="ch5.lt32" class="half_rhythm"><div>Change in creatinine</div></li></ul></td><td headers="hd_h_ch5.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mixed population; 65% had received previous medication</td></tr><tr><td headers="hd_h_ch5.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<b>Dahlof 2005 (PIXCEL trial)</b>
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<a class="bibr" href="#ch5.ref47" rid="ch5.ref47">
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<sup>47</sup>
|
|
</a>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Combination:</p>
|
|
<p>Perindopril 2 mg plus indapamide 0.625 mg (n=341)</p>
|
|
<p>Monotherapy:</p>
|
|
<p>Enalapril 10 mg (n=338)</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hypertension with or without type 2 diabetes (n=679)</td><td headers="hd_h_ch5.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">At 12 months:
|
|
<ul id="ch5.l6"><li id="ch5.lt33" class="half_rhythm"><div>Discontinuation due to adverse events</div></li></ul></td><td headers="hd_h_ch5.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Number of participants with type 2 diabetes not specified</td></tr><tr><td headers="hd_h_ch5.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Mogensen 2003 (PREMIER trial)</b>
|
|
<a class="bibr" href="#ch5.ref148" rid="ch5.ref148">
|
|
<sup>148</sup>
|
|
</a>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Combination:</p>
|
|
<p>Perindopril 2 mg plus indapamide 0.625 mg (n=237)</p>
|
|
<p>Monotherapy:</p>
|
|
<p>Enalapril 10 mg (n=244)</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hypertension with type 2 diabetes (n=481)</td><td headers="hd_h_ch5.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">At 12 months
|
|
<ul id="ch5.l7"><li id="ch5.lt34" class="half_rhythm"><div>Serious cardiovascular events</div></li><li id="ch5.lt35" class="half_rhythm"><div>Change in creatinine clearance</div></li><li id="ch5.lt36" class="half_rhythm"><div>Discontinuation due to adverse events</div></li><li id="ch5.lt37" class="half_rhythm"><div>Hypotension</div></li></ul></td><td headers="hd_h_ch5.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5tab3"><div id="ch5.tab3" class="table"><h3><span class="label">Table 3</span><span class="title">Clinical evidence summary: monotherapy versus combination (adults with hypertension and type 2 diabetes strata)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.tab3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.tab3_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch5.tab3_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_ch5.tab3_1_1_1_1" style="text-align:left;vertical-align:bottom;">Outcomes</th><th id="hd_h_ch5.tab3_1_1_1_2" rowspan="2" colspan="1" headers="hd_h_ch5.tab3_1_1_1_2" style="text-align:left;vertical-align:bottom;">No of Participants (studies) Follow up</th><th id="hd_h_ch5.tab3_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_ch5.tab3_1_1_1_3" style="text-align:left;vertical-align:bottom;">Quality of the evidence (GRADE)</th><th id="hd_h_ch5.tab3_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_ch5.tab3_1_1_1_4" style="text-align:left;vertical-align:bottom;">Relative effect (95% CI)</th><th id="hd_h_ch5.tab3_1_1_1_5" colspan="2" rowspan="1" style="text-align:left;vertical-align:bottom;">Anticipated absolute effects</th></tr><tr><th headers="hd_h_ch5.tab3_1_1_1_5" id="hd_h_ch5.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Risk with Control</th><th headers="hd_h_ch5.tab3_1_1_1_5" id="hd_h_ch5.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Risk difference with Combination versus monotherapy (95% CI)</th></tr></thead><tbody><tr><td headers="hd_h_ch5.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Serious cardiovascular events</td><td headers="hd_h_ch5.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>481</p>
|
|
<p>(1 study)</p>
|
|
<p>12 months</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>VERY LOW<sup>1</sup><sup>,</sup><sup>2</sup><sup>,</sup><sup>3</sup></p>
|
|
<p>due to risk of bias, indirectness, imprecision</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 0.39</p>
|
|
<p>(0.15 to 0.98)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">63 per 1,000</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">39 fewer per 1,000 (from 1 fewer to 54 fewer)</td></tr><tr><td headers="hd_h_ch5.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Change in creatinine clearance (ml/min)</td><td headers="hd_h_ch5.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>481</p>
|
|
<p>(1 study)</p>
|
|
<p>12 months</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>LOW<sup>1</sup></p>
|
|
<p>due to risk of bias</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The mean change in creatinine in the control group was −4.8</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The mean change in creatinine in the intervention groups was 0.7 higher (1.19 lower to 2.59 higher)</td></tr><tr><td headers="hd_h_ch5.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Discontinuation due to adverse events</td><td headers="hd_h_ch5.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>481</p>
|
|
<p>(1 study)</p>
|
|
<p>12 months</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>VERY LOW<sup>1</sup><sup>,</sup><sup>3</sup></p>
|
|
<p>due to risk of bias, imprecision</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 0.88</p>
|
|
<p>(0.49 to 1.59)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">89 per 1,000</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">11 fewer per 1,000 (from 47 fewer to 50 more)</td></tr><tr><td headers="hd_h_ch5.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Discontinuation due to adverse events<sup>6</sup></td><td headers="hd_h_ch5.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>538</p>
|
|
<p>(1 study)</p>
|
|
<p>12 months</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>VERY LOW<sup>1</sup><sup>,</sup>
|
|
<sup>3</sup><sup>,</sup>
|
|
<sup>4</sup></p>
|
|
<p>due to risk of bias, imprecision, indirectness</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.21</p>
|
|
<p>(0.41 to 3.56)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">22 per 1,000</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5 more per 1,000 (from 13 fewer to 54 more)</td></tr><tr><td headers="hd_h_ch5.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dizziness (hypotension)</td><td headers="hd_h_ch5.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>481</p>
|
|
<p>(1 study)</p>
|
|
<p>12 months</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>VERY LOW<sup>1</sup><sup>,</sup><sup>3</sup><sup>,</sup>
|
|
<sup>5</sup></p>
|
|
<p>due to risk of bias, imprecision, indirectness</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 0.58</p>
|
|
<p>(0.14 to 2.41)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21 per 1,000</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9 fewer per 1,000 (from 18 fewer to 30 more)</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1</dt><dd><div id="ch5.tab3_1"><p class="no_margin">Downgraded by 1 increment if the majority of the evidence was at high risk of bias and downgraded by 2 increments if the majority of the evidence was at very high risk of bias</p></div></dd></dl><dl class="bkr_refwrap"><dt>2</dt><dd><div id="ch5.tab3_2"><p class="no_margin">Downgraded by 1 increment because the majority of the evidence had indirect outcomes</p></div></dd></dl><dl class="bkr_refwrap"><dt>3</dt><dd><div id="ch5.tab3_3"><p class="no_margin">Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4</dt><dd><div id="ch5.tab3_4"><p class="no_margin">Downgraded by 1 increment because the majority of the evidence had an indirect population</p></div></dd></dl><dl class="bkr_refwrap"><dt>5</dt><dd><div id="ch5.tab3_5"><p class="no_margin">Downgraded by 1 increment because the majority of the evidence had indirect outcomes; unclear if dizziness related to hypotension</p></div></dd></dl><dl class="bkr_refwrap"><dt>6</dt><dd><div id="ch5.tab3_6"><p class="no_margin">Mixed population (including people with type 2 diabetes)</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobch5tab4"><div id="ch5.tab4" class="table"><h3><span class="label">Table 4</span><span class="title">Clinical evidence summary: monotherapy versus combination (adults with hypertension and without type 2 diabetes strata)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.tab4/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.tab4_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch5.tab4_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_ch5.tab4_1_1_1_1" style="text-align:left;vertical-align:bottom;">Outcomes</th><th id="hd_h_ch5.tab4_1_1_1_2" rowspan="2" colspan="1" headers="hd_h_ch5.tab4_1_1_1_2" style="text-align:left;vertical-align:bottom;">No of Participants (studies) Follow up</th><th id="hd_h_ch5.tab4_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_ch5.tab4_1_1_1_3" style="text-align:left;vertical-align:bottom;">Quality of the evidence (GRADE)</th><th id="hd_h_ch5.tab4_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_ch5.tab4_1_1_1_4" style="text-align:left;vertical-align:bottom;">Relative effect (95% CI)</th><th id="hd_h_ch5.tab4_1_1_1_5" colspan="2" rowspan="1" style="text-align:left;vertical-align:bottom;">Anticipated absolute effects</th></tr><tr><th headers="hd_h_ch5.tab4_1_1_1_5" id="hd_h_ch5.tab4_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Risk with Control</th><th headers="hd_h_ch5.tab4_1_1_1_5" id="hd_h_ch5.tab4_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Risk difference with Combination versus monotherapy (95% CI)</th></tr></thead><tbody><tr><td headers="hd_h_ch5.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Change in creatinine (μmol/L)</td><td headers="hd_h_ch5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>457</p>
|
|
<p>(1 study)</p>
|
|
<p>12 months</p>
|
|
</td><td headers="hd_h_ch5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HIGH</td><td headers="hd_h_ch5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_ch5.tab4_1_1_1_5 hd_h_ch5.tab4_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The mean change in creatinine in the control group was 1.7</td><td headers="hd_h_ch5.tab4_1_1_1_5 hd_h_ch5.tab4_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The mean change in creatinine in the intervention groups was 2.3 higher (0.7 to 3.9 higher)</td></tr><tr><td headers="hd_h_ch5.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Discontinuation due to adverse events</td><td headers="hd_h_ch5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>418</p>
|
|
<p>(1 study)</p>
|
|
<p>12 months</p>
|
|
</td><td headers="hd_h_ch5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>VERY LOW<sup>1</sup><sup>,</sup><sup>2</sup></p>
|
|
<p>due to risk of bias, imprecision</p>
|
|
</td><td headers="hd_h_ch5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 0.89</p>
|
|
<p>(0.49 to 1.62)</p>
|
|
</td><td headers="hd_h_ch5.tab4_1_1_1_5 hd_h_ch5.tab4_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">99 per 1,000</td><td headers="hd_h_ch5.tab4_1_1_1_5 hd_h_ch5.tab4_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">11 fewer per 1,000 (from 52 fewer to 58 more)</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1</dt><dd><div id="ch5.tab4_1"><p class="no_margin">Downgraded by 1 increment if the majority of the evidence was at high risk of bias and downgraded by 2 increments if the majority of the evidence was at very high risk of bias</p></div></dd></dl><dl class="bkr_refwrap"><dt>2</dt><dd><div id="ch5.tab4_2"><p class="no_margin">Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobch5tab5"><div id="ch5.tab5" class="table"><h3><span class="label">Table 5</span><span class="title">UK costs of anti-hypertensives (monotherapies or combinations)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.tab5/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.tab5_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Drug</th><th id="hd_h_ch5.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Detail</th><th id="hd_h_ch5.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Daily dose</th><th id="hd_h_ch5.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cost/ month (£)</th><th id="hd_h_ch5.tab5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cost/year (£)</th></tr></thead><tbody><tr><th headers="hd_h_ch5.tab5_1_1_1_1 hd_h_ch5.tab5_1_1_1_2 hd_h_ch5.tab5_1_1_1_3 hd_h_ch5.tab5_1_1_1_4 hd_h_ch5.tab5_1_1_1_5" id="hd_b_ch5.tab5_1_1_1_1" colspan="5" rowspan="1" style="text-align:left;vertical-align:middle;">Monotherapies</th></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Perindopril erbumine</p>
|
|
<p>(ACE inhibitor)</p>
|
|
</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>2 mg tablets, pack of 30</p>
|
|
<p>= £1.86</p>
|
|
</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2 mg</td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£1.89</td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£22.63</td></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Enalapril maleate</p>
|
|
<p>(ACE inhibitor)</p>
|
|
</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>10 mg tablets, pack of 28</p>
|
|
<p>= £1.53</p>
|
|
</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10 mg<sup>(a)</sup></td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£1.66</td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£19.94</td></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Atenolol</p>
|
|
<p>(Beta blocker)</p>
|
|
</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>50 mg tablets, pack of 28</p>
|
|
<p>= £0.54</p>
|
|
</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">50 mg</td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£0.59</td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£7.04</td></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Losartan</p>
|
|
<p>(ARB)</p>
|
|
</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>50 mg tablets, pack of 28</p>
|
|
<p>= £0.82</p>
|
|
</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">50 mg<sup>(b)</sup></td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£0.89</td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£10.69</td></tr><tr><th headers="hd_h_ch5.tab5_1_1_1_1 hd_h_ch5.tab5_1_1_1_2 hd_h_ch5.tab5_1_1_1_3 hd_h_ch5.tab5_1_1_1_4 hd_h_ch5.tab5_1_1_1_5" id="hd_b_ch5.tab5_1_1_6_1" colspan="5" rowspan="1" style="text-align:left;vertical-align:middle;">Combination</th></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Perindopril erbumine</p>
|
|
<p>(ACE inhibitor)</p>
|
|
<p>and</p>
|
|
</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>2 mg tablets, pack of 30</p>
|
|
<p>= £1.86</p>
|
|
</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2 mg</td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£1.89</td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£22.63</td></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Indapamide</p>
|
|
<p>(thiazide)</p>
|
|
</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1.5 mg tablets, pack of 30</p>
|
|
<p>= £3.40</p>
|
|
</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1.5 mg<sup>(c)</sup></td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£3.45</td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<u>£41.37</u>
|
|
</td></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<i>Separate pills</i>
|
|
</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£64.00</td></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Losartan and hydrochlorothiazide <i>single pill</i></td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>50 mg Losartan, 12.5 mg thiazide, pack of 28</p>
|
|
<p>= £1.13</p>
|
|
</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">50 mg Losartan, 12.5 mg thiazide<sup>(b)</sup></td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£1.23</td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£14.73</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Source: BNF (Drug Tariff price)<a class="bibr" href="#ch5.ref27" rid="ch5.ref27"><sup>27</sup></a>, DATE: 03 May 2019.</p></div></dd></dl><dl class="bkr_refwrap"><dt>(a)</dt><dd><div id="ch5.tab5_1"><p class="no_margin">Dose from clinical review</p></div></dd></dl><dl class="bkr_refwrap"><dt>(b)</dt><dd><div id="ch5.tab5_2"><p class="no_margin">Clinical review 100 mg but used 50 mg here as combination was 50 mg so comparing the same dose in monotherapy and combination.</p></div></dd></dl><dl class="bkr_refwrap"><dt>(c)</dt><dd><div id="ch5.tab5_3"><p class="no_margin">Clinical review used 2 mg perindopril and 0.625 mg indapamide but these doses weren’t available in the BNF.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobch5tab6"><div id="ch5.tab6" class="table"><h3><span class="label">Table 6</span><span class="title">Costs of hospitalisation from cardiovascular events</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.tab6/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.tab6_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch5.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">HRG code</th><th id="hd_h_ch5.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HRG code description</th><th id="hd_h_ch5.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Weighted average cost</th></tr></thead><tbody><tr><td headers="hd_h_ch5.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>EB10A to EB10E</p>
|
|
<p>Myocardial infarction</p>
|
|
</td><td headers="hd_h_ch5.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Actual or Suspected Myocardial Infarction, with CC Score 13+</p>
|
|
<p>Actual or Suspected Myocardial Infarction, with CC Score 10–12</p>
|
|
<p>Actual or Suspected Myocardial Infarction, with CC Score 7–9</p>
|
|
<p>Actual or Suspected Myocardial Infarction, with CC Score 4–6</p>
|
|
<p>Actual or Suspected Myocardial Infarction, with CC Score 0–3</p>
|
|
</td><td headers="hd_h_ch5.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£1,515</td></tr><tr><td headers="hd_h_ch5.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>AA35A to AA35F</p>
|
|
<p>Stroke</p>
|
|
</td><td headers="hd_h_ch5.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Stroke with CC Score 16+</p>
|
|
<p>Stroke with CC Score 13–15</p>
|
|
<p>Stroke with CC Score 10–12</p>
|
|
<p>Stroke with CC Score 7–9</p>
|
|
<p>Stroke with CC Score 4–6</p>
|
|
<p>Stroke with CC Score 0–3</p>
|
|
</td><td headers="hd_h_ch5.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£3,339</td></tr><tr><td headers="hd_h_ch5.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>EB13A to EB13D</p>
|
|
<p>Angina</p>
|
|
</td><td headers="hd_h_ch5.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Angina with CC Score 12+</p>
|
|
<p>Angina with CC Score 8–11</p>
|
|
<p>Angina with CC Score 4–7</p>
|
|
<p>Angina with CC Score 0–3</p>
|
|
</td><td headers="hd_h_ch5.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£716</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>(a)</dt><dd><div id="ch5.tab6_1"><p class="no_margin">From NHS reference costs 2017/18, total Healthcare resource group (HRG) schedule. {NHS Improvement, 2018 #1855}</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobch5tab7"><div id="ch5.tab7" class="table"><h3><span class="label">Table 7</span><span class="title">Cost trade-off illustration</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.tab7/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.tab7_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Intervention</th><th id="hd_h_ch5.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Drug cost (per 1000)<sup>(a)</sup></th><th id="hd_h_ch5.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Cardiovascular events (per 1000)<sup>(b)</sup></th><th id="hd_h_ch5.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Cardiovascular event cost</th><th id="hd_h_ch5.tab7_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Total cost</th></tr></thead><tbody><tr><th headers="hd_h_ch5.tab7_1_1_1_1 hd_h_ch5.tab7_1_1_1_2 hd_h_ch5.tab7_1_1_1_3 hd_h_ch5.tab7_1_1_1_4 hd_h_ch5.tab7_1_1_1_5" id="hd_b_ch5.tab7_1_1_1_1" colspan="5" rowspan="1" style="text-align:left;vertical-align:middle;">CV event = MI</th></tr><tr><td headers="hd_h_ch5.tab7_1_1_1_1 hd_b_ch5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monotherapy</td><td headers="hd_h_ch5.tab7_1_1_1_2 hd_b_ch5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">£19,945</td><td headers="hd_h_ch5.tab7_1_1_1_3 hd_b_ch5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">63</td><td headers="hd_h_ch5.tab7_1_1_1_4 hd_b_ch5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">£95,436</td><td headers="hd_h_ch5.tab7_1_1_1_5 hd_b_ch5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">£115,381</td></tr><tr><td headers="hd_h_ch5.tab7_1_1_1_1 hd_b_ch5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dual therapy</td><td headers="hd_h_ch5.tab7_1_1_1_2 hd_b_ch5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">£63,997</td><td headers="hd_h_ch5.tab7_1_1_1_3 hd_b_ch5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">25</td><td headers="hd_h_ch5.tab7_1_1_1_4 hd_b_ch5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">£37,220</td><td headers="hd_h_ch5.tab7_1_1_1_5 hd_b_ch5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">£101,217</td></tr><tr><th headers="hd_h_ch5.tab7_1_1_1_1 hd_h_ch5.tab7_1_1_1_2 hd_h_ch5.tab7_1_1_1_3 hd_h_ch5.tab7_1_1_1_4 hd_h_ch5.tab7_1_1_1_5" id="hd_b_ch5.tab7_1_1_4_1" colspan="5" rowspan="1" style="text-align:left;vertical-align:middle;">CV event = Stroke</th></tr><tr><td headers="hd_h_ch5.tab7_1_1_1_1 hd_b_ch5.tab7_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monotherapy</td><td headers="hd_h_ch5.tab7_1_1_1_2 hd_b_ch5.tab7_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">£19,945</td><td headers="hd_h_ch5.tab7_1_1_1_3 hd_b_ch5.tab7_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">63</td><td headers="hd_h_ch5.tab7_1_1_1_4 hd_b_ch5.tab7_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">£210,382</td><td headers="hd_h_ch5.tab7_1_1_1_5 hd_b_ch5.tab7_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">£230,327</td></tr><tr><td headers="hd_h_ch5.tab7_1_1_1_1 hd_b_ch5.tab7_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dual therapy</td><td headers="hd_h_ch5.tab7_1_1_1_2 hd_b_ch5.tab7_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">£63,997</td><td headers="hd_h_ch5.tab7_1_1_1_3 hd_b_ch5.tab7_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">25</td><td headers="hd_h_ch5.tab7_1_1_1_4 hd_b_ch5.tab7_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">£82,049</td><td headers="hd_h_ch5.tab7_1_1_1_5 hd_b_ch5.tab7_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">£146,046</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>(a)</dt><dd><div id="ch5.tab7_1"><p class="no_margin">12 month cost as clinical studies were over a 12 month period.</p></div></dd></dl><dl class="bkr_refwrap"><dt>(b)</dt><dd><div id="ch5.tab7_2"><p class="no_margin">Data taken from the clinical review</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobch5appatab1"><div id="ch5.appa.tab1" class="table"><h3><span class="label">Table 8</span><span class="title">Review protocol: Step 1 antihypertensive treatment</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.appa.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appa.tab1_lrgtbl__"><table><thead><tr><th id="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Field</th><th id="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Content</th></tr></thead><tbody><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Review question</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Is monotherapy or combination antihypertensive therapy more clinically and cost effective for step 1 treatment for hypertension in adults?</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Type of review question</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Intervention review</p>
|
|
<p>A review of health economic evidence related to the same review question was conducted in parallel with this review. For details, see the health economic review protocol for this NICE guideline.</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Objective of the review</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">To establish whether monotherapy or combination therapy is most clinically and cost effective as a step 1 treatment for primary hypertension</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Eligibility criteria – population / disease / condition / issue / domain</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Population: Adults (over 18 years) with primary hypertension who are not on current pharmacological treatment for hypertension (minimum wash-out 4 weeks)</p>
|
|
<p>Stratify by presence or absence of type 2 diabetes</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Eligibility criteria – intervention(s) / exposure(s) / prognostic factor(s)</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Antihypertensive pharmacological combination therapy received for a minimum of 1 year (either adjunct or non-adjunct, defined as 2 antihypertensive medications prescribed simultaneously – may be in 1 pill or 2). Examples include:
|
|
<ul id="ch5.l9"><li id="ch5.lt39" class="half_rhythm"><div>ACE inhibitor and CCB</div></li><li id="ch5.lt40" class="half_rhythm"><div>ARB and CCB</div></li><li id="ch5.lt41" class="half_rhythm"><div>ACE inhibitor and diuretic (thiazide-like or conventional)</div></li><li id="ch5.lt42" class="half_rhythm"><div>ARB and diuretic (thiazide-like or conventional)</div></li><li id="ch5.lt43" class="half_rhythm"><div>ACE inhibitor and CCB (Trandolapril and verapamil; TARKA)</div></li><li id="ch5.lt44" class="half_rhythm"><div>Beta blocker and CCB (atenolol and nifedipine)</div></li><li id="ch5.lt45" class="half_rhythm"><div>Beta blocker and thiazides (atenolol and chlortalidone; timolol and bendroflumethiazide)</div></li><li id="ch5.lt46" class="half_rhythm"><div>Non-thiazide and thiazide (amiloride and hydrochlorothiazide)</div></li></ul></td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Eligibility criteria – comparator(s) / control or reference (gold) standard</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Antihypertensive pharmacological monotherapy received for a minimum of 1 year. Examples include:
|
|
<ul id="ch5.l10"><li id="ch5.lt47" class="half_rhythm"><div>ACE inhibitor</div></li><li id="ch5.lt48" class="half_rhythm"><div>Low-cost ARB</div></li><li id="ch5.lt49" class="half_rhythm"><div>Thiazide-like diuretic (such as chlortalidone or indapamide)</div></li><li id="ch5.lt50" class="half_rhythm"><div>Conventional thiazide diuretic (such as bendroflumethiazide or hydrochlorothiazide)</div></li><li id="ch5.lt51" class="half_rhythm"><div>CCB</div></li><li id="ch5.lt52" class="half_rhythm"><div>Beta-blockers</div></li><li id="ch5.lt53" class="half_rhythm"><div>Aliskiren (direct renin inhibitors)</div></li><li id="ch5.lt54" class="half_rhythm"><div>Doxazosin, prazosin, terazosin, (alpha blockers)</div></li><li id="ch5.lt55" class="half_rhythm"><div>Clonidine, moxonidine, methyldopa (centrally acting antihypertensive)</div></li></ul></td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes and prioritisation</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">All outcomes to be measured at a minimum of 12 months. Where multiple time points are reported within each study, the longest time point only will be extracted.
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<ul id="ch5.l11"><li id="ch5.lt56" class="half_rhythm"><div>All-cause mortality</div></li><li id="ch5.lt57" class="half_rhythm"><div>Health-related quality of life</div></li><li id="ch5.lt58" class="half_rhythm"><div>Stroke (ischaemic or haemorrhagic)</div></li><li id="ch5.lt59" class="half_rhythm"><div>MI</div></li></ul><b>Important</b>
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<ul id="ch5.l12"><li id="ch5.lt60" class="half_rhythm"><div>Heart failure needing hospitalisation</div></li><li id="ch5.lt61" class="half_rhythm"><div>(including lower limb, coronary and carotid artery procedures)Angina needing hospitalisation</div></li><li id="ch5.lt62" class="half_rhythm"><div>Side effect 1: Acute kidney injury</div></li><li id="ch5.lt63" class="half_rhythm"><div>Side effect 2: New onset diabetes</div></li><li id="ch5.lt64" class="half_rhythm"><div>Side effect 3: Change in creatinine or eGFR</div></li><li id="ch5.lt65" class="half_rhythm"><div>Side effect 4: Hypotension (dizziness)</div></li><li id="ch5.lt66" class="half_rhythm"><div>Discontinuation or dose reduction due to side effects</div></li><li id="ch5.lt67" class="half_rhythm"><div>[Combined cardiovascular disease outcomes in the absence of MI and stroke data]</div></li><li id="ch5.lt68" class="half_rhythm"><div>[Coronary heart disease outcome in the absence of MI data]</div></li></ul></td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Eligibility criteria – study design</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RCTs and SRs</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Other inclusion exclusion criteria</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Minimum follow up time: 1 year</p>
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<p>Exclusions:
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<ul id="ch5.l13"><li id="ch5.lt69" class="half_rhythm"><div>Studies including participants with type 1 diabetes or chronic kidney disease (A3 or above [heavy proteinuria]); for type 2 diabetes strata studies including participants with A2 or above (heavy proteinuria).</div></li><li id="ch5.lt70" class="half_rhythm"><div>Indirect populations with secondary causes of hypertension such as tumours or structural vascular defects (Conn’s adenoma, phaeochromocytoma, renovascular hypertension)</div></li><li id="ch5.lt71" class="half_rhythm"><div>Pregnant women</div></li><li id="ch5.lt72" class="half_rhythm"><div>Crossover trials (unless washout is ≥ 4 weeks)</div></li><li id="ch5.lt73" class="half_rhythm"><div>Children (younger than 18 years)</div></li></ul></p>
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</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Proposed sensitivity / subgroup analysis, or meta-regression</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Subgroups for analysis of heterogeneity:
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<ul id="ch5.l14"><li id="ch5.lt74" class="half_rhythm"><div>Age (75 as a cut off)*</div></li><li id="ch5.lt75" class="half_rhythm"><div>Family origin (African and Caribbean, White, South Asian)</div></li><li id="ch5.lt76" class="half_rhythm"><div>Severity (moderate [stage 1 BP 140–59/90–99] versus high [stage 2 BP 160/100])</div></li></ul>*To note that we will also extract evidence in those aged over 80 if this evidence is reported separately.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Selection process – duplicate screening / selection / analysis</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">A senior research fellow will undertake quality assurance prior to completion.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Data management (software)</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Pairwise meta-analyses will be performed using Cochrane Review Manager (RevMan5).</p>
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<p>GRADEpro will be used to assess the quality of evidence for each outcome.</p>
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<p>Endnote will be used for bibliography, citations, sifting and reference management.</p>
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</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Information sources – databases and dates</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Medline, Embase, the Cochrane Library</p>
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<p>Language: Restrict to English only</p>
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<p>Key papers:</p>
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<p>Cochrane review (2017): <a href="http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010316.pub2/full" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">http:<wbr style="display:inline-block"></wbr>​//onlinelibrary<wbr style="display:inline-block"></wbr>​.wiley.com/doi/10.1002/14651858<wbr style="display:inline-block"></wbr>​.CD010316.pub2/full</a></p>
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</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Identify if an update</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Yes, 2011</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Author contacts</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="https://www.nice.org.uk/guidance/cg127" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://www<wbr style="display:inline-block"></wbr>​.nice.org.uk/guidance/cg127</a>
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</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Highlight if amendment to previous protocol</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details, please see section 4.5 of <a href="https://www.nice.org.uk/article/pmg20/chapter/4-Developing-review-questions-and-planning-the-evidence-review#planning-the-evidence-review" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Search strategy – for 1 database</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details, please see <a href="#ch5.appb">appendix B</a></td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Data collection process – forms / duplicate</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">A standardised evidence table format will be used, and published as <a href="#ch5.appd">appendix D</a> of the evidence report.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Data items – define all variables to be collected</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details, please see evidence tables in <a href="#ch5.appd">appendix D</a> (clinical evidence tables) or <a href="#ch5.apph">H</a> (health economic evidence tables).</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Methods for assessing bias at outcome / study level</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Standard study checklists were used to appraise critically individual studies. For details, please see section 6.2 of <a href="https://www.nice.org.uk/article/pmg20/chapter/6-Reviewing-research-evidence#assessing-the-quality-of-the-evidence" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a></p>
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<p>The risk of bias across all available evidence was evaluated for each outcome using an adaptation of the ‘Grading of Recommendations Assessment, Development and Evaluation (GRADE) toolbox’ developed by the international GRADE working group <a href="http://www.gradeworkinggroup.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">http://www<wbr style="display:inline-block"></wbr>​.gradeworkinggroup.org/</a></p>
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</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Criteria for quantitative synthesis</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details, please see section 6.4 of <a href="https://www.nice.org.uk/article/pmg20/chapter/6-Reviewing-research-evidence#assessing-the-quality-of-the-evidence" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Methods for quantitative analysis – combining studies and exploring (in)consistency</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details, please see the separate Methods report for this guideline.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Meta-bias assessment – publication bias, selective reporting bias</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details, please see section 6.2 of <a href="https://www.nice.org.uk/article/pmg20/chapter/6-Reviewing-research-evidence#assessing-the-quality-of-the-evidence" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Confidence in cumulative evidence</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details, please see sections 6.4 and 9.1 of <a href="https://www.nice.org.uk/article/pmg20/chapter/1-Introduction-and-overview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Rationale / context – what is known</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details, please see the introduction to the evidence review.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Describe contributions of authors and guarantor</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>A <a href="https://www.nice.org.uk/guidance/indevelopment/gid-ng10054/documents" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">multidisciplinary committee</a> developed the evidence review. The committee was convened by the National Guideline Centre (NGC) and chaired by Anthony Wierzbicki in line with section 3 of <a href="https://www.nice.org.uk/article/pmg20/chapter/1%20Introduction%20and%20overview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>.</p>
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<p>Staff from the NGC undertook systematic literature searches, appraised the evidence, conducted meta-analysis and cost-effectiveness analysis where appropriate, and drafted the evidence review in collaboration with the committee. For details, please see <a href="https://www.nice.org.uk/article/pmg20/chapter/1-Introduction-and-overview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>.</p>
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</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sources of funding / support</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The NGC is funded by NICE and hosted by the Royal College of Physicians.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Name of sponsor</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The NGC is funded by NICE and hosted by the Royal College of Physicians.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Roles of sponsor</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NICE funds the NGC to develop guidelines for those working in the NHS, public health and social care in England.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">PROSPERO registration number</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not registered</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5appatab2"><div id="ch5.appa.tab2" class="table"><h3><span class="label">Table 9</span><span class="title">Health economic review protocol</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.appa.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appa.tab2_lrgtbl__"><table><thead><tr><th id="hd_h_ch5.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Review question</th><th id="hd_h_ch5.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">All questions – health economic evidence</th></tr></thead><tbody><tr><td headers="hd_h_ch5.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<b>Objectives</b>
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</td><td headers="hd_h_ch5.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">To identify health economic studies relevant to any of the review questions.</td></tr><tr><td headers="hd_h_ch5.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<b>Search criteria</b>
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</td><td headers="hd_h_ch5.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul id="ch5.l15"><li id="ch5.lt77" class="half_rhythm"><div>Populations, interventions and comparators must be as specified in the clinical review protocol above.</div></li><li id="ch5.lt78" class="half_rhythm"><div>Studies must be of a relevant health economic study design (cost–utility analysis, cost-effectiveness analysis, cost–benefit analysis, cost–consequences analysis, comparative cost analysis).</div></li><li id="ch5.lt79" class="half_rhythm"><div>Studies must not be a letter, editorial or commentary, or a review of health economic evaluations. (Recent reviews will be ordered although not reviewed. The bibliographies will be checked for relevant studies, which will then be ordered.)</div></li><li id="ch5.lt80" class="half_rhythm"><div>Unpublished reports will not be considered unless submitted as part of a call for evidence.</div></li><li id="ch5.lt81" class="half_rhythm"><div>Studies must be in English.</div></li></ul></td></tr><tr><td headers="hd_h_ch5.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<b>Search strategy</b>
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</td><td headers="hd_h_ch5.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">A health economic study search will be undertaken using population-specific terms and a health economic study filter – see <a href="#ch5.appb">appendix B</a> below. No date cut-off from the previous guideline was used.</td></tr><tr><td headers="hd_h_ch5.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<b>Review strategy</b>
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</td><td headers="hd_h_ch5.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Studies not meeting any of the search criteria above will be excluded. Studies published before 2002, abstract-only studies and studies from non-OECD countries or the US will also be excluded.</p>
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<p>Studies published after 2002 that were included in the previous guideline(s) will be reassessed for inclusion and may be included or selectively excluded based on their relevance to the questions covered in this update and whether more applicable evidence is also identified.</p>
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<p>Each remaining study will be assessed for applicability and methodological limitations using the NICE economic evaluation checklist which can be found in <a href="#ch5.apph">appendix H</a> of Developing NICE guidelines: the manual (2014).<a class="bibr" href="#ch5.ref155" rid="ch5.ref155"><sup>155</sup></a></p>
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<p><b>Inclusion and exclusion criteria</b>
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<ul id="ch5.l16"><li id="ch5.lt82" class="half_rhythm"><div>If a study is rated as both ‘Directly applicable’ and with ‘Minor limitations’, then it will be included in the guideline. A health economic evidence table will be completed and it will be included in the health economic evidence profile.</div></li><li id="ch5.lt83" class="half_rhythm"><div>If a study is rated as either ‘Not applicable’ or with ‘Very serious limitations’, then it will usually be excluded from the guideline. If it is excluded then a health economic evidence table will not be completed and it will not be included in the health economic evidence profile.</div></li><li id="ch5.lt84" class="half_rhythm"><div>If a study is rated as ‘Partially applicable’, with ‘Potentially serious limitations’ or both, then there is discretion over whether it should be included.</div></li></ul></p>
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<p>
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<b>Where there is discretion</b>
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</p>
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<p>The health economist will make a decision based on the relative applicability and quality of the available evidence for that question in discussion with the guideline committee if required. The ultimate aim is to include health economic studies that are helpful for decision-making in the context of the guideline and the current NHS setting. If several studies are considered of sufficiently high applicability and methodological quality that they could all be included, then the health economist, in discussion with the committee if required, may decide to include only the most applicable studies and to exclude selectively the remaining studies. All studies excluded based on applicability or methodological limitations will be listed with explanation in the excluded health economic studies appendix below.</p>
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<p>The health economist will be guided by the following hierarchies.</p>
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<p><i>Setting:</i>
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<ul id="ch5.l17"><li id="ch5.lt85" class="half_rhythm"><div>UK NHS (most applicable).</div></li><li id="ch5.lt86" class="half_rhythm"><div>OECD countries with predominantly public health insurance systems (for example, France, Germany, Sweden).</div></li><li id="ch5.lt87" class="half_rhythm"><div>OECD countries with predominantly private health insurance systems (for example, Switzerland).</div></li><li id="ch5.lt88" class="half_rhythm"><div>Studies set in non-OECD countries or in the US will be excluded before being assessed for applicability and methodological limitations.</div></li></ul></p>
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<p><i>Health economic study type:</i>
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<ul id="ch5.l18"><li id="ch5.lt89" class="half_rhythm"><div>Cost–utility analysis (most applicable).</div></li><li id="ch5.lt90" class="half_rhythm"><div>Other type of full economic evaluation (cost–benefit analysis, cost-effectiveness analysis, cost–consequences analysis).</div></li><li id="ch5.lt91" class="half_rhythm"><div>Comparative cost analysis.</div></li><li id="ch5.lt92" class="half_rhythm"><div>Non-comparative cost analyses including cost-of-illness studies will be excluded before being assessed for applicability and methodological limitations.</div></li></ul></p>
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<p><i>Year of analysis:</i>
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<ul id="ch5.l19"><li id="ch5.lt93" class="half_rhythm"><div>The more recent the study, the more applicable it will be.</div></li><li id="ch5.lt94" class="half_rhythm"><div>Studies published in 2002 or later (including any such studies included in the previous guideline[s]) but that depend on unit costs and resource data entirely or predominantly before 2002 will be rated as ‘Not applicable’.</div></li><li id="ch5.lt95" class="half_rhythm"><div>Studies published before 2002 (including any such studies included in the previous guideline[s]) will be excluded before being assessed for applicability and methodological limitations.</div></li></ul></p>
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<p><i>Quality and relevance of effectiveness data used in the health economic analysis:</i>
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<ul id="ch5.l20"><li id="ch5.lt96" class="half_rhythm"><div>The more closely the clinical effectiveness data used in the health economic analysis match with the outcomes of the studies included in the clinical review, the more useful the analysis will be for decision-making in the guideline.</div></li><li id="ch5.lt97" class="half_rhythm"><div>Generally, economic evaluations based on excludes from the clinical review will be excluded.</div></li></ul></p>
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</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5appbtab1"><div id="ch5.appb.tab1" class="table"><h3><span class="label">Table 10</span><span class="title">Database date parameters and filters used</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.appb.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appb.tab1_lrgtbl__"><table><thead><tr><th id="hd_h_ch5.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Database</th><th id="hd_h_ch5.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dates searched</th><th id="hd_h_ch5.appb.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Search filter used</th></tr></thead><tbody><tr><td headers="hd_h_ch5.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Medline (OVID)</td><td headers="hd_h_ch5.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1946–02 October 2018</td><td headers="hd_h_ch5.appb.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Exclusions</p>
|
|
<p>Randomised controlled trials</p>
|
|
<p>Systematic review studies</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Embase (OVID)</td><td headers="hd_h_ch5.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1974–02 October 2018</td><td headers="hd_h_ch5.appb.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Exclusions</p>
|
|
<p>Randomised controlled trials</p>
|
|
<p>Systematic review studies</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The Cochrane Library (Wiley)</td><td headers="hd_h_ch5.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Cochrane Reviews to Issue 8 of 12, August 2018</p>
|
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<p>CENTRAL to Issue 7 of 12, July 2018</p>
|
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<p>DARE and NHS EED to Issue 2 of 4, April 2015</p>
|
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<p>HTA to Issue 4 of 4, October 2016</p>
|
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</td><td headers="hd_h_ch5.appb.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">None</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5appbtab2"><div id="ch5.appb.tab2" class="table"><h3><span class="label">Table 11</span><span class="title">Medline (Ovid) search terms</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.appb.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appb.tab2_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Hypertension/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">hypertens*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(elevat* adj2 blood adj pressur*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(high adj blood adj pressur*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(increase* adj2 blood pressur*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((systolic or diastolic or arterial) adj2 pressur*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/1–6</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">8.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp pregnancy/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Hypertension, Pregnancy-Induced/ not exp Hypertension/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(pre eclampsia or pre-eclampsia or preeclampsia).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">11.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Hypertension, Portal/ not exp Hypertension/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">12.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Hypertension, Pulmonary/ not exp Hypertension/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Intracranial Hypertension/ not exp Hypertension/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">14.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Ocular Hypertension/ not exp Hypertension/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Diabetes Mellitus, Type 1/ not exp Diabetes Mellitus, Type 2/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">16.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/9–15</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">17.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7 not 16</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">18.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">letter/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">19.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">editorial/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">20.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">news/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp historical article/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">22.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Anecdotes as Topic/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">23.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">comment/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">24.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">case report/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">25.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(letter or comment*).ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/18–25</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">27.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomized controlled trial/ or random*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">28.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26 not 27</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">29.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">animals/ not humans/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">30.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Animals, Laboratory/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">31.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Animal Experimentation/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">32.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Models, Animal/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">33.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Rodentia/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">34.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(rat or rats or mouse or mice).ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">35.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/28–34</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">36.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">17 not 35</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">37.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(exp child/ or exp pediatrics/ or exp infant/) not (exp adolescent/ or exp adult/ or exp middle age/ or exp aged/)</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">38.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">36 not 37</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">39.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">limit 38 to English language</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">40.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Drug Combinations/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">41.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Drug Therapy, Combination/ or *Drug Therapy/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">42.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">drug therap*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">43.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((combination* or combined or multiple or single) adj (therap* or agent* or drug* or treatment*)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">44.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(monotherap* or mono therap*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">45.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/40–44</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">46.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">39 and 45</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">47.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Angiotensin-Converting Enzyme Inhibitors/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">48.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Angiotensin-converting enzyme inhibitor*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">49.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(ACE inhibitor* or ACEI).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">50.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Captopril or Enalapril or Fosinopril or Imidapril or Lisinopril or Moexipril or Perindopril or Quinapril or Ramipril or Trandolapril or Capoten or Ecopace or Noyada or Innovace or Tanatril or Zestril or Perdix or Coversil or Accupro or Tritace).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">51.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Calcium Channel Blockers/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">52.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Calcium channel blocker*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">53.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CCB.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">54.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Amlodipine or Clevidipine or Diltiazem or Felodipine or Isradipine or Lacidipine or Lercanidipine or Nicardipine or Nifedipine or Verapamil or Amlostin or Istin or Adizem or Angitil or Dilcardia or Dilzem or Slozem or Tildiem or Viazem or Zemtard or Kenzem or Cardioplen or Felendil or Neofel or Parmid or Plendil or Pinefeld or Vascalpha or Molap or Motens or Zanidip or Cardene or Adalat or Adipine or Coracten or Fortipine or Nifedipress or Tensipine or Valni or Securon or Verapress or Vertab or Univer or Zolvera or Cleviprex).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">55.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Angiotensin Receptor Antagonists/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">56.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Angiotensin II adj3 (antagonist* or blocker*)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">57.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ARB.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">58.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Azilsartan or Candesartan or Eprosartan or Irbesartan or Losartan or Olmesartan or Telmisartan or Valsartan or Edarbi or Amias or Teveten or Aprovel or Ifirmasta or Sabervel or Cozaar or Olmetec or Tolura or Micardis or Diovan).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">59.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Diuretics/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">60.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Diuretics, Thiazide/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">61.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((thiazide or thiazide-like or non-thiazide or conventional or potassium sparing) adj3 diuretic*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">62.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Amiloride or Cyclopenthiazide or Spironolactone or Bendroflumethiazide or Hydrochlorothiazide or Co-amilozide or Co-triamterzide or Co-zidocapt or Chlortalidone or Indapamide or Metolazone or Xipamide or Carace or Zestoretic or Coversyl or Accuretic or Cozaar or Sevikar or Olmetec or Actelsar or Tolucombi or Co-Diovan or Hygroton or Co-tenidone or Kalspare or Natrilix or Cardide or Indipam or Rawel or Tensaid or Alkapamid or Zaroxolyn or Diurexan or Aprinox or Neo-Naclex or CoAprovel or Lisoretic or Dyazide or Navispare or Lasilactone).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">63.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Adrenergic beta-Antagonists/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">64.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(adrenergic beta antagonist* or beta blocker* or b blocker*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">65.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Carvedilol or Labetalol or Atenolol or Nadolol or Oxprenolol or Pindolol or Propranolol or Timolol or Acebutolol or Bisoprolol or Celiprolol or Esmolol or Metoprolol or Nebivolol or Carvedilol or Tenormin or Tenif or Corgard or Slow-Trasicor or Visken or Viskladix or Bedranol or Beta-Prograne or Syprol or Betim or Sectral or Cardicor or Congescor or Celectol or Breviblock or Betaloc or Lopresor or Nebilet).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">66.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Adrenergic alpha-Antagonists/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">67.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(adrenergic alpha antagonist* or alpha adrenoreceptor blocker* or alpha blocker*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">68.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Doxazosin or Prazosin or Terazosin or Cardura or Doxadura or Raporsin or Slocinx or Doxzogen or Larbex or Hypovase or Hytrin).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">69.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Antihypertensive Agents/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">70.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">centrally acting antihypertensive*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">71.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Clonidine or Moxonidine or Methyldopa or Catapres or Dixarit or Aldomet or Physiotens).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">72.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">renin inhibitor*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">73.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Aliskiren or Rasilez).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">74.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((trandolapril and verapamil) or TARKA).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">75.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/47–74</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">76.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">46 and 75</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">77.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomized controlled trial.pt.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">78.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">controlled clinical trial.pt.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">79.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomi#ed.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">80.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">placebo.ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">81.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomly.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">82.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Clinical Trials as topic.sh.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">83.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">trial.ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">84.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/77–83</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">85.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Meta-Analysis/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">86.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Meta-Analysis as Topic/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">87.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(meta analy* or metanaly* or metaanaly* or meta regression).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">88.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((systematic* or evidence*) adj3 (review* or overview*)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">89.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(reference list* or bibliograph* or hand search* or manual search* or relevant journals).ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">90.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(search strategy or search criteria or systematic search or study selection or data extraction).ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">91.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(search* adj4 literature).ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">92.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(medline or pubmed or cochrane or embase or psychlit or psyclit or psychinfo or psycinfo or cinahl or science citation index or bids or cancerlit).ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">93.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">cochrane.jw.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">94.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((multiple treatment* or indirect or mixed) adj2 comparison*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">95.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/85–94</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">96.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">76 and (84 or 95)</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5appbtab3"><div id="ch5.appb.tab3" class="table"><h3><span class="label">Table 12</span><span class="title">Embase (Ovid) search terms</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.appb.tab3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appb.tab3_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Hypertension/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">hypertens*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(essential adj hypertension).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(isolat* adj hypertension).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(elevat* adj2 blood adj pressur*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(high adj blood adj pressur*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(increase* adj2 blood pressur*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">8.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((systolic or diastolic or arterial) adj2 pressur*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/1–8</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp pregnancy/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">11.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Maternal Hypertension/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">12.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(pre eclampsia or pre-eclampsia or preeclampsia).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Hypertension, Portal/ not exp Hypertension/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">14.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Hypertension, Pulmonary/ not exp Hypertension/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Intracranial Hypertension/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">16.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Ocular Hypertension/ not exp Hypertension/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">17.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Diabetes Mellitus, Type 1/ not exp Diabetes Mellitus, Type 2/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">18.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/10–17</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">19.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9 not 18</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">20.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">letter.pt. or letter/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">note.pt.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">22.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">editorial.pt.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">23.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">case report/ or case study/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">24.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(letter or comment*).ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">25.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/20–24</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomized controlled trial/ or random*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">27.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">25 not 26</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">28.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">animal/ not human/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">29.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">nonhuman/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">30.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Animal Experiment/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">31.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Experimental Animal/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">32.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">animal model/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">33.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Rodent/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">34.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(rat or rats or mouse or mice).ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">35.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/27–34</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">36.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">19 not 35</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">37.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(exp child/ or exp pediatrics/) not (exp adult/ or exp adolescent/)</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">38.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">36 not 37</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">39.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">limit 38 to English language</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">40.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Drug Combinations/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">41.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">*Therapy/ or *Drug Therapy/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">42.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">drug therap*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">43.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((combination* or combined or multiple or single) adj (therap* or agent* or drug* or treatment*)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">44.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(monotherap* or mono therap*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">45.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/40–44</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">46.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">39 and 45</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">47.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp *Angiotensin-Converting Enzyme Inhibitors/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">48.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Angiotensin-converting enzyme inhibitor*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">49.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(ACE inhibitor* or ACEI).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">50.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Captopril or Enalapril or Fosinopril or Imidapril or Lisinopril or Moexipril or Perindopril or Quinapril or Ramipril or Trandolapril or Capoten or Ecopace or Noyada or Innovace or Tanatril or Zestril or Perdix or Coversil or Accupro or Tritace).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">51.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp *Calcium Channel Blockers/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">52.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Calcium channel blocker*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">53.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CCB.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">54.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Amlodipine or Clevidipine or Diltiazem or Felodipine or Isradipine or Lacidipine or Lercanidipine or Nicardipine or Nifedipine or Verapamil or Amlostin or Istin or Adizem or Angitil or Dilcardia or Dilzem or Slozem or Tildiem or Viazem or Zemtard or Kenzem or Cardioplen or Felendil or Neofel or Parmid or Plendil or Pinefeld or Vascalpha or Molap or Motens or Zanidip or Cardene or Adalat or Adipine or Coracten or Fortipine or Nifedipress or Tensipine or Valni or Securon or Verapress or Vertab or Univer or Zolvera or Cleviprex).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">55.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp *Angiotensin Receptor Antagonists/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">56.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Angiotensin II adj3 (antagonist* or blocker*)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">57.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ARB.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">58.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Azilsartan or Candesartan or Eprosartan or Irbesartan or Losartan or Olmesartan or Telmisartan or Valsartan or Edarbi or Amias or Teveten or Aprovel or Ifirmasta or Sabervel or Cozaar or Olmetec or Tolura or Micardis or Diovan).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">59.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Diuretics/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">60.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Diuretics, Thiazide/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">61.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((thiazide or thiazide-like or non-thiazide or conventional or potassium sparing) adj3 diuretic*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">62.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Amiloride or Cyclopenthiazide or Spironolactone or Bendroflumethiazide or Hydrochlorothiazide or Co-amilozide or Co-triamterzide or Co-zidocapt or Chlortalidone or Indapamide or Metolazone or Xipamide or Carace or Zestoretic or Coversyl or Accuretic or Cozaar or Sevikar or Olmetec or Actelsar or Tolucombi or Co-Diovan or Hygroton or Co-tenidone or Kalspare or Natrilix or Cardide or Indipam or Rawel or Tensaid or Alkapamid or Zaroxolyn or Diurexan or Aprinox or Neo-Naclex or CoAprovel or Lisoretic or Dyazide or Navispare or Lasilactone).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">63.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">*Adrenergic beta-Antagonists/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">64.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(adrenergic beta antagonist* or beta blocker* or b blocker*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">65.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Carvedilol or Labetalol or Atenolol or Nadolol or Oxprenolol or Pindolol or Propranolol or Timolol or Acebutolol or Bisoprolol or Celiprolol or Esmolol or Metoprolol or Nebivolol or Carvedilol or Tenormin or Tenif or Corgard or Slow-Trasicor or Visken or Viskladix or Bedranol or Beta-Prograne or Syprol or Betim or Sectral or Cardicor or Congescor or Celectol or Breviblock or Betaloc or Lopresor or Nebilet).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">66.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp *Adrenergic alpha-Antagonists/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">67.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(adrenergic alpha antagonist* or alpha adrenoreceptor blocker* or alpha blocker*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">68.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Doxazosin or Prazosin or Terazosin or Cardura or Doxadura or Raporsin or Slocinx or Doxzogen or Larbex or Hypovase or Hytrin).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">69.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">*Antihypertensive Agents/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">70.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">centrally acting antihypertensive*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">71.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Clonidine or Moxonidine or Methyldopa or Catapres or Dixarit or Aldomet or Physiotens).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">72.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">renin inhibitor*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">73.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Aliskiren or Rasilez).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">74.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((trandolapril and verapamil) or TARKA).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">75.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/47–74</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">76.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">46 and 75</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">77.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">random*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">78.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">factorial*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">79.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(crossover* or cross over*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">80.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((doubl* or singl*) adj blind*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">81.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(assign* or allocat* or volunteer* or placebo*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">82.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">crossover procedure/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">83.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">single blind procedure/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">84.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomized controlled trial/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">85.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">double blind procedure/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">86.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/77–85</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">87.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">systematic review/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">88.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">meta-analysis/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">89.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(meta analy* or metanaly* or metaanaly* or meta regression).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">90.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((systematic* or evidence*) adj3 (review* or overview*)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">91.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(reference list* or bibliograph* or hand search* or manual search* or relevant journals).ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">92.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(search strategy or search criteria or systematic search or study selection or data extraction).ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">93.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(search* adj4 literature).ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">94.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(medline or pubmed or cochrane or embase or psychlit or psyclit or psychinfo or psycinfo or cinahl or science citation index or bids or cancerlit).ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">95.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">cochrane.jw.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">96.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((multiple treatment* or indirect or mixed) adj2 comparison*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">97.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/87–96</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">98.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">76 and (86 or 97)</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5appbtab4"><div id="ch5.appb.tab4" class="table"><h3><span class="label">Table 13</span><span class="title">Cochrane Library (Wiley) search terms</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.appb.tab4/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appb.tab4_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#1.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Hypertension] explode all trees</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#2.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">hypertens*:ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#3.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(elevat* near/2 blood next pressur*):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#4.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(high near/1 blood near/1 pressur*):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#5.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(increase* near/2 blood pressur*):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#6.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((systolic or diastolic or arterial) near/2 pressur*):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#7.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(or #1-#6)</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#8.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Angiotensin-Converting Enzyme Inhibitors] explode all trees</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#9.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Angiotensin-converting enzyme inhibitor*:ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#10.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(ACE inhibitor* or ACEI):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#11.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Captopril or Enalapril or Fosinopril or Imidapril or Lisinopril or Moexipril or Perindopril or Quinapril or Ramipril or Trandolapril or Capoten or Ecopace or Noyada or Innovace or Tanatril or Zestril or Perdix or Coversil or Accupro or Tritace):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#12.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Calcium Channel Blockers] explode all trees</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#13.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Calcium channel blocker*:ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#14.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CCB:ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#15.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Amlodipine or Clevidipine or Diltiazem or Felodipine or Isradipine or Lacidipine or Lercanidipine or Nicardipine or Nifedipine or Verapamil or Amlostin or Istin or Adizem or Angitil or Dilcardia or Dilzem or Slozem or Tildiem or Viazem or Zemtard or Kenzem or Cardioplen or Felendil or Neofel or Parmid or Plendil or Pinefeld or Vascalpha or Molap or Motens or Zanidip or Cardene or Adalat or Adipine or Coracten or Fortipine or Nifedipress or Tensipine or Valni or Securon or Verapress or Vertab or Univer or Zolvera or Cleviprex):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#16.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Angiotensin Receptor Antagonists] explode all trees</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#17.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(AngiotensinII near/3 (antagonist* or blocker*)):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#18.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ARB:ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#19.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Azilsartan or Candesartan or Eprosartan or Irbesartan or Losartan or Olmesartan or Telmisartan or Valsartan or Edarbi or Amias or Teveten or Aprovel or Ifirmasta or Sabervel or Cozaar or Olmetec or Tolura or Micardis or Diovan):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#20.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Diuretics] this term only</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#21.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Sodium Chloride Symporter Inhibitors] this term only</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#22.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((thiazide or thiazide-like or non-thiazide or conventional or potassium sparing) near/3 diuretic*):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#23.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Amiloride or Cyclopenthiazide or Spironolactone or Bendroflumethiazide or Hydrochlorothiazide or Co-amilozide or Co-triamterzide or Co-zidocapt or Chlortalidone or Indapamide or Metolazone or Xipamide or Carace or Zestoretic or Coversyl or Accuretic or Cozaar or Sevikar or Olmetec or Actelsar or Tolucombi or Co-Diovan or Hygroton or Co-tenidone or Kalspare or Natrilix or Cardide or Indipam or Rawel or Tensaid or Alkapamid or Zaroxolyn or Diurexan or Aprinox or Neo-Naclex or CoAprovel or Lisoretic or Dyazide or Navispare or Lasilactone):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#24.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Adrenergic beta-Antagonists] this term only</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#25.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(adrenergic beta antagonist* or beta blocker* or b blocker*):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#26.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Carvedilol or Labetalol or Atenolol or Nadolol or Oxprenolol or Pindolol or Propranolol or Timolol or Acebutolol or Bisoprolol or Celiprolol or Esmolol or Metoprolol or Nebivolol or Carvedilol or Tenormin or Tenif or Corgard or Slow-Trasicor or Visken or Viskladix or Bedranol or Beta-Prograne or Syprol or Betim or Sectral or Cardicor or Congescor or Celectol or Breviblock or Betaloc or Lopresor or Nebilet):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#27.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Adrenergic alpha-Antagonists] explode all trees</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#28.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(adrenergic alpha antagonist* or alpha adrenoreceptor blocker* or alpha blocker*):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#29.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Doxazosin or Prazosin or Terazosin or Cardura or Doxadura or Raporsin or Slocinx or Doxzogen or Larbex or Hypovase or Hytrin):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#30.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Antihypertensive Agents] this term only</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#31.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">centrally acting antihypertensive*:ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#32.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Clonidine or Moxonidine or Methyldopa or Catapres or Dixarit or Aldomet or Physiotens):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#33.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">renin inhibitor*:ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#34.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Aliskiren or Rasilez):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#35.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((trandolapril and verapamil) or TARKA):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#36.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(or #8-#35)</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#37.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#7 and #36</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#38.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Drug Combinations] this term only</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#39.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Drug Therapy, Combination] this term only</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#40.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Drug Therapy] this term only</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#41.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">drug therap*:ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#42.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((combination* or combined or multiple or single) near/1 (therap* or agent* or drug* or treatment*)):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#43.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(monotherap* or mono therap*):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#44.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(or #38-#43)</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#45.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#37 and #44</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5appbtab5"><div id="ch5.appb.tab5" class="table"><h3><span class="label">Table 14</span><span class="title">Database date parameters and filters used</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.appb.tab5/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appb.tab5_lrgtbl__"><table><thead><tr><th id="hd_h_ch5.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Database</th><th id="hd_h_ch5.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dates searched</th><th id="hd_h_ch5.appb.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Search filter used</th></tr></thead><tbody><tr><td headers="hd_h_ch5.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Medline</td><td headers="hd_h_ch5.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2014–28 August 2018</td><td headers="hd_h_ch5.appb.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Exclusions</p>
|
|
<p>Health economics studies</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Embase</td><td headers="hd_h_ch5.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2014–28 August 2018</td><td headers="hd_h_ch5.appb.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Exclusions</p>
|
|
<p>Health economics studies</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Centre for Research and Dissemination (CRD)</td><td headers="hd_h_ch5.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>HTA - Inception–28 August 2018</p>
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<p>NHS EED - Inception to March 2015</p>
|
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</td><td headers="hd_h_ch5.appb.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">None</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5appbtab6"><div id="ch5.appb.tab6" class="table"><h3><span class="label">Table 15</span><span class="title">Medline (Ovid) search terms</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.appb.tab6/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appb.tab6_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">exp Hypertension/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">hypertens*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(elevat* adj2 blood adj pressur*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(high adj blood adj pressur*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(increase* adj2 blood pressur*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">6.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">((systolic or diastolic or arterial) adj2 pressur*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">7.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">or/1–6</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">8.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">letter/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">9.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">editorial/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">news/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">11.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">exp historical article/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">12.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Anecdotes as Topic/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">13.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">comment/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">14.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">case report/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">15.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(letter or comment*).ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">16.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">or/8–15</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">17.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">randomized controlled trial/ or random*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">18.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">16 not 17</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">19.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">animals/ not humans/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">20.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">exp Animals, Laboratory/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">21.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">exp Animal Experimentation/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">22.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">exp Models, Animal/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">23.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">exp Rodentia/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">24.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(rat or rats or mouse or mice).ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">25.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">or/18–24</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">26.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">7 not 25</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">27.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">limit 26 to English language</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">28.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Economics/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">29.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Value of life/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">30.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">exp “Costs and Cost Analysis”/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">31.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">exp Economics, Hospital/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">32.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">exp Economics, Medical/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">33.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Economics, Nursing/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">34.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Economics, Pharmaceutical/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">35.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">exp “Fees and Charges”/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">36.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">exp Budgets/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">37.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">budget*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">38.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">cost*.ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">39.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(economic* or pharmaco?economic*).ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">40.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(price* or pricing*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">41.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(cost* adj2 (effective* or utilit* or benefit* or minimi* or unit* or estimat* or variable*)).ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">42.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(financ* or fee or fees).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">43.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(value adj2 (money or monetary)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">44.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">or/28–43</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">45.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">27 and 44</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5appbtab7"><div id="ch5.appb.tab7" class="table"><h3><span class="label">Table 16</span><span class="title">Embase (Ovid) search terms</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.appb.tab7/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appb.tab7_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">exp Hypertension/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">hypertens*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(elevat* adj2 blood adj pressur*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(high adj blood adj pressur*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">5.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(increase* adj2 blood pressur*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">6.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">((systolic or diastolic or arterial) adj2 pressur*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">7.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">or/1–6</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">8.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">letter.pt. or letter/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">9.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">note.pt.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">editorial.pt.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">11.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">case report/ or case study/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">12.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(letter or comment*).ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">13.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">or/8–12</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">14.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">randomized controlled trial/ or random*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">15.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">13 not 14</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">16.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">animal/ not human/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">17.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">nonhuman/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">18.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">exp Animal Experiment/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">19.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">exp Experimental Animal/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">20.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">animal model/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">21.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">exp Rodent/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">22.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(rat or rats or mouse or mice).ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">23.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">or/15–22</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">24.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">7 not 23</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">25.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">limit 24 to English language</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">26.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">health economics/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">27.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">exp economic evaluation/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">28.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">exp health care cost/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">29.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">exp fee/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">30.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">budget/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">31.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">funding/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">32.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">budget*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">33.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">cost*.ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">34.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(economic* or pharmaco?economic*).ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">35.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(price* or pricing*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">36.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(cost* adj2 (effective* or utilit* or benefit* or minimi* or unit* or estimat* or variable*)).ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">37.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(financ* or fee or fees).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">38.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(value adj2 (money or monetary)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">39.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">or/26–38</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">40.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">25 and 39</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5appbtab8"><div id="ch5.appb.tab8" class="table"><h3><span class="label">Table 17</span><span class="title">NHS EED and HTA (CRD) search terms</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.appb.tab8/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appb.tab8_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">#1.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MeSH DESCRIPTOR Hypertension EXPLODE ALL TREES IN NHSEED,HTA</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">#2.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(Hypertens*) IN NHSEED, HTA</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">#3.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(elevat* adj2 blood adj pressur*) IN NHSEED, HTA</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">#4.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(high adj blood adj pressur*) IN NHSEED, HTA</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">#5.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">(increase* adj2 blood pressur*) IN NHSEED, HTA</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">#6.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">((systolic or diastolic or arterial) adj2 pressur*) IN NHSEED, HTA</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">#7.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">#1 OR #2 OR #3 OR #4 OR #5 OR #6</td></tr></tbody></table></div></div></article><article data-type="fig" id="figobch5appcfig1"><div id="ch5.appc.fig1" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%201.%20Flow%20chart%20of%20clinical%20study%20selection%20for%20the%20review%20of%20step%201%20antihypertensive%20treatment.&p=BOOKS&id=578061_ch5appcf1.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK578061/bin/ch5appcf1.jpg" alt="Figure 1. Flow chart of clinical study selection for the review of step 1 antihypertensive treatment." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 1</span><span class="title">Flow chart of clinical study selection for the review of step 1 antihypertensive treatment</span></h3></div></article><article data-type="fig" id="figobch5appefig1"><div id="ch5.appe.fig1" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%202.%20Serious%20cardiovascular%20events%20at%2012%20months.&p=BOOKS&id=578061_ch5appef1.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK578061/bin/ch5appef1.jpg" alt="Figure 2. Serious cardiovascular events at 12 months." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 2</span><span class="title">Serious cardiovascular events at 12 months</span></h3></div></article><article data-type="fig" id="figobch5appefig2"><div id="ch5.appe.fig2" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%203.%20Change%20in%20creatinine%20at%2012%20months.&p=BOOKS&id=578061_ch5appef2.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK578061/bin/ch5appef2.jpg" alt="Figure 3. Change in creatinine at 12 months." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 3</span><span class="title">Change in creatinine at 12 months</span></h3></div></article><article data-type="fig" id="figobch5appefig3"><div id="ch5.appe.fig3" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%204.%20Discontinuation%20due%20to%20adverse%20events%20at%2012%20months.&p=BOOKS&id=578061_ch5appef3.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK578061/bin/ch5appef3.jpg" alt="Figure 4. Discontinuation due to adverse events at 12 months." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 4</span><span class="title">Discontinuation due to adverse events at 12 months</span></h3></div></article><article data-type="fig" id="figobch5appefig4"><div id="ch5.appe.fig4" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%205.%20Discontinuation%20due%20to%20adverse%20events%20at%2012%20months%20(including%20type%202%20diabetes).&p=BOOKS&id=578061_ch5appef4.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK578061/bin/ch5appef4.jpg" alt="Figure 5. Discontinuation due to adverse events at 12 months (including type 2 diabetes)." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 5</span><span class="title">Discontinuation due to adverse events at 12 months (including type 2 diabetes)</span></h3></div></article><article data-type="fig" id="figobch5appefig5"><div id="ch5.appe.fig5" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%206.%20Hypotension%20(dizziness)%20at%2012%20months.&p=BOOKS&id=578061_ch5appef5.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK578061/bin/ch5appef5.jpg" alt="Figure 6. Hypotension (dizziness) at 12 months." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 6</span><span class="title">Hypotension (dizziness) at 12 months</span></h3></div></article><article data-type="fig" id="figobch5appefig6"><div id="ch5.appe.fig6" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%207.%20Change%20in%20creatinine%20(%003BCmol%2FL)%20at%2012%20months.&p=BOOKS&id=578061_ch5appef6.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK578061/bin/ch5appef6.jpg" alt="Figure 7. Change in creatinine (μmol/L) at 12 months." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 7</span><span class="title">Change in creatinine (μmol/L) at 12 months</span></h3></div></article><article data-type="fig" id="figobch5appefig7"><div id="ch5.appe.fig7" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%208.%20Discontinuation%20due%20to%20adverse%20events%20at%2012%20months.&p=BOOKS&id=578061_ch5appef7.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK578061/bin/ch5appef7.jpg" alt="Figure 8. Discontinuation due to adverse events at 12 months." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 8</span><span class="title">Discontinuation due to adverse events at 12 months</span></h3></div></article><article data-type="table-wrap" id="figobch5appftab1"><div id="ch5.appf.tab1" class="table"><h3><span class="label">Table 18</span><span class="title">Clinical evidence profile: combination versus monotherapy in adults with primary hypertension and type 2 diabetes</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.appf.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appf.tab1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch5.appf.tab1_1_1_1_1" colspan="7" rowspan="1" style="text-align:center;vertical-align:middle;">Quality assessment</th><th id="hd_h_ch5.appf.tab1_1_1_1_2" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">No of patients</th><th id="hd_h_ch5.appf.tab1_1_1_1_3" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Effect</th><th id="hd_h_ch5.appf.tab1_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_ch5.appf.tab1_1_1_1_4" style="text-align:center;vertical-align:middle;">Quality</th><th id="hd_h_ch5.appf.tab1_1_1_1_5" rowspan="2" colspan="1" headers="hd_h_ch5.appf.tab1_1_1_1_5" style="text-align:center;vertical-align:middle;">Importance</th></tr><tr><th headers="hd_h_ch5.appf.tab1_1_1_1_1" id="hd_h_ch5.appf.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No of studies</th><th headers="hd_h_ch5.appf.tab1_1_1_1_1" id="hd_h_ch5.appf.tab1_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Design</th><th headers="hd_h_ch5.appf.tab1_1_1_1_1" id="hd_h_ch5.appf.tab1_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk of bias</th><th headers="hd_h_ch5.appf.tab1_1_1_1_1" id="hd_h_ch5.appf.tab1_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inconsistency</th><th headers="hd_h_ch5.appf.tab1_1_1_1_1" id="hd_h_ch5.appf.tab1_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Indirectness</th><th headers="hd_h_ch5.appf.tab1_1_1_1_1" id="hd_h_ch5.appf.tab1_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Imprecision</th><th headers="hd_h_ch5.appf.tab1_1_1_1_1" id="hd_h_ch5.appf.tab1_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Other considerations</th><th headers="hd_h_ch5.appf.tab1_1_1_1_2" id="hd_h_ch5.appf.tab1_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Combination versus monotherapy</th><th headers="hd_h_ch5.appf.tab1_1_1_1_2" id="hd_h_ch5.appf.tab1_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Control</th><th headers="hd_h_ch5.appf.tab1_1_1_1_3" id="hd_h_ch5.appf.tab1_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Relative (95% CI)</th><th headers="hd_h_ch5.appf.tab1_1_1_1_3" id="hd_h_ch5.appf.tab1_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Absolute</th></tr></thead><tbody><tr><th headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_h_ch5.appf.tab1_1_1_2_3 hd_h_ch5.appf.tab1_1_1_2_4 hd_h_ch5.appf.tab1_1_1_2_5 hd_h_ch5.appf.tab1_1_1_2_6 hd_h_ch5.appf.tab1_1_1_2_7 hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_h_ch5.appf.tab1_1_1_2_9 hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_h_ch5.appf.tab1_1_1_2_11 hd_h_ch5.appf.tab1_1_1_1_4 hd_h_ch5.appf.tab1_1_1_1_5" id="hd_b_ch5.appf.tab1_1_1_1_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:middle;">Serious cardiovascular events (follow-up 12 months)</th></tr><tr><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_3 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>1</sup></td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_4 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_5 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>2</sup></td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_6 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>3</sup></td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_7 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>6/244</p>
|
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<p>(2.5%)</p>
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</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_9 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>15/237</p>
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<p>(6.3%)</p>
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</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">RR 0.39 (0.15 to 0.98)</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_11 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">39 fewer per 1000 (from 1 fewer to 54 fewer)</td><td headers="hd_h_ch5.appf.tab1_1_1_1_4 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>⨁◯◯◯</p>
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<p>VERY LOW</p>
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</td><td headers="hd_h_ch5.appf.tab1_1_1_1_5 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CRITICAL</td></tr><tr><th headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_h_ch5.appf.tab1_1_1_2_3 hd_h_ch5.appf.tab1_1_1_2_4 hd_h_ch5.appf.tab1_1_1_2_5 hd_h_ch5.appf.tab1_1_1_2_6 hd_h_ch5.appf.tab1_1_1_2_7 hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_h_ch5.appf.tab1_1_1_2_9 hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_h_ch5.appf.tab1_1_1_2_11 hd_h_ch5.appf.tab1_1_1_1_4 hd_h_ch5.appf.tab1_1_1_1_5" id="hd_b_ch5.appf.tab1_1_1_3_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:middle;">Change in creatinine (ml/min; follow-up 12 months; Better indicated by lower values)</th></tr><tr><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_3 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious<sup>1</sup></td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_4 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_5 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_6 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious imprecision</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_7 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">237</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_9 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">244</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_11 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MD 0.7 higher (1.19 lower to 2.59 higher)</td><td headers="hd_h_ch5.appf.tab1_1_1_1_4 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>⨁⨁◯◯</p>
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<p>LOW</p>
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</td><td headers="hd_h_ch5.appf.tab1_1_1_1_5 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_h_ch5.appf.tab1_1_1_2_3 hd_h_ch5.appf.tab1_1_1_2_4 hd_h_ch5.appf.tab1_1_1_2_5 hd_h_ch5.appf.tab1_1_1_2_6 hd_h_ch5.appf.tab1_1_1_2_7 hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_h_ch5.appf.tab1_1_1_2_9 hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_h_ch5.appf.tab1_1_1_2_11 hd_h_ch5.appf.tab1_1_1_1_4 hd_h_ch5.appf.tab1_1_1_1_5" id="hd_b_ch5.appf.tab1_1_1_5_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:middle;">Discontinuation due to adverse events (follow-up 12 months)</th></tr><tr><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_3 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>1</sup></td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_4 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_5 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_6 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious<sup>3</sup></td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_7 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
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<p>19/244</p>
|
|
<p>(7.8%)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_9 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>21/237</p>
|
|
<p>(8.9%)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">RR 0.88 (0.49 to 1.59)</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_11 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">11 fewer per 1000 (from 47 fewer to 50 more)</td><td headers="hd_h_ch5.appf.tab1_1_1_1_4 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
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<p>⨁◯◯◯</p>
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<p>VERY LOW</p>
|
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</td><td headers="hd_h_ch5.appf.tab1_1_1_1_5 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_h_ch5.appf.tab1_1_1_2_3 hd_h_ch5.appf.tab1_1_1_2_4 hd_h_ch5.appf.tab1_1_1_2_5 hd_h_ch5.appf.tab1_1_1_2_6 hd_h_ch5.appf.tab1_1_1_2_7 hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_h_ch5.appf.tab1_1_1_2_9 hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_h_ch5.appf.tab1_1_1_2_11 hd_h_ch5.appf.tab1_1_1_1_4 hd_h_ch5.appf.tab1_1_1_1_5" id="hd_b_ch5.appf.tab1_1_1_7_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:middle;">Discontinuation due to adverse events – overall strata (follow-up 12 months)</th></tr><tr><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_3 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>1</sup></td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_4 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_5 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Serious<sup>4</sup></td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_6 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious<sup>3</sup></td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_7 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>7/264</p>
|
|
<p>(2.7%)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_9 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
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<p>6/274</p>
|
|
<p>(2.2%)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">RR 1.21 (0.41 to 3.56)</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_11 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5 more per 1000 (from 13 fewer to 54 more)</td><td headers="hd_h_ch5.appf.tab1_1_1_1_4 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>⨁◯◯◯</p>
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<p>VERY LOW</p>
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</td><td headers="hd_h_ch5.appf.tab1_1_1_1_5 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_h_ch5.appf.tab1_1_1_2_3 hd_h_ch5.appf.tab1_1_1_2_4 hd_h_ch5.appf.tab1_1_1_2_5 hd_h_ch5.appf.tab1_1_1_2_6 hd_h_ch5.appf.tab1_1_1_2_7 hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_h_ch5.appf.tab1_1_1_2_9 hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_h_ch5.appf.tab1_1_1_2_11 hd_h_ch5.appf.tab1_1_1_1_4 hd_h_ch5.appf.tab1_1_1_1_5" id="hd_b_ch5.appf.tab1_1_1_9_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:middle;">Dizziness (hypotension; follow-up 12 months)</th></tr><tr><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_3 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>1</sup></td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_4 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_5 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Serious<sup>5</sup></td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_6 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious<sup>3</sup></td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_7 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>3/244</p>
|
|
<p>(1.2%)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_9 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>5/237</p>
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|
<p>(2.1%)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">RR 0.58 (0.14 to 2.41)</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_11 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">9 fewer per 1000 (from 18 fewer to 30 more)</td><td headers="hd_h_ch5.appf.tab1_1_1_1_4 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>⨁◯◯◯</p>
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<p>VERY LOW</p>
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</td><td headers="hd_h_ch5.appf.tab1_1_1_1_5 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IMPORTANT</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1</dt><dd><div id="ch5.appf.tab1_1"><p class="no_margin">Downgraded by 1 increment if the majority of the evidence was at high risk of bias and downgraded by 2 increments if the majority of the evidence was at very high risk of bias</p></div></dd></dl><dl class="bkr_refwrap"><dt>2</dt><dd><div id="ch5.appf.tab1_2"><p class="no_margin">Downgraded by 1 increment because the majority of the evidence had indirect outcomes</p></div></dd></dl><dl class="bkr_refwrap"><dt>3</dt><dd><div id="ch5.appf.tab1_3"><p class="no_margin">Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4</dt><dd><div id="ch5.appf.tab1_4"><p class="no_margin">Downgraded by 1 increment because the majority of the evidence had an indirect population</p></div></dd></dl><dl class="bkr_refwrap"><dt>5</dt><dd><div id="ch5.appf.tab1_5"><p class="no_margin">Downgraded by 1 increment because the majority of the evidence had indirect outcomes; unclear if dizziness related to hypotension</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobch5appftab2"><div id="ch5.appf.tab2" class="table"><h3><span class="label">Table 19</span><span class="title">Clinical evidence profile: combination versus monotherapy in adults with primary hypertension and without type 2 diabetes</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.appf.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appf.tab2_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch5.appf.tab2_1_1_1_1" colspan="7" rowspan="1" style="text-align:center;vertical-align:middle;">Quality assessment</th><th id="hd_h_ch5.appf.tab2_1_1_1_2" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">No of patients</th><th id="hd_h_ch5.appf.tab2_1_1_1_3" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Effect</th><th id="hd_h_ch5.appf.tab2_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_ch5.appf.tab2_1_1_1_4" style="text-align:center;vertical-align:middle;">Quality</th><th id="hd_h_ch5.appf.tab2_1_1_1_5" rowspan="2" colspan="1" headers="hd_h_ch5.appf.tab2_1_1_1_5" style="text-align:center;vertical-align:middle;">Importance</th></tr><tr><th headers="hd_h_ch5.appf.tab2_1_1_1_1" id="hd_h_ch5.appf.tab2_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No of studies</th><th headers="hd_h_ch5.appf.tab2_1_1_1_1" id="hd_h_ch5.appf.tab2_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Design</th><th headers="hd_h_ch5.appf.tab2_1_1_1_1" id="hd_h_ch5.appf.tab2_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk of bias</th><th headers="hd_h_ch5.appf.tab2_1_1_1_1" id="hd_h_ch5.appf.tab2_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inconsistency</th><th headers="hd_h_ch5.appf.tab2_1_1_1_1" id="hd_h_ch5.appf.tab2_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Indirectness</th><th headers="hd_h_ch5.appf.tab2_1_1_1_1" id="hd_h_ch5.appf.tab2_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Imprecision</th><th headers="hd_h_ch5.appf.tab2_1_1_1_1" id="hd_h_ch5.appf.tab2_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Other considerations</th><th headers="hd_h_ch5.appf.tab2_1_1_1_2" id="hd_h_ch5.appf.tab2_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Combination versus monotherapy</th><th headers="hd_h_ch5.appf.tab2_1_1_1_2" id="hd_h_ch5.appf.tab2_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Control</th><th headers="hd_h_ch5.appf.tab2_1_1_1_3" id="hd_h_ch5.appf.tab2_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Relative (95% CI)</th><th headers="hd_h_ch5.appf.tab2_1_1_1_3" id="hd_h_ch5.appf.tab2_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Absolute</th></tr></thead><tbody><tr><th headers="hd_h_ch5.appf.tab2_1_1_1_1 hd_h_ch5.appf.tab2_1_1_2_1 hd_h_ch5.appf.tab2_1_1_2_2 hd_h_ch5.appf.tab2_1_1_2_3 hd_h_ch5.appf.tab2_1_1_2_4 hd_h_ch5.appf.tab2_1_1_2_5 hd_h_ch5.appf.tab2_1_1_2_6 hd_h_ch5.appf.tab2_1_1_2_7 hd_h_ch5.appf.tab2_1_1_1_2 hd_h_ch5.appf.tab2_1_1_2_8 hd_h_ch5.appf.tab2_1_1_2_9 hd_h_ch5.appf.tab2_1_1_1_3 hd_h_ch5.appf.tab2_1_1_2_10 hd_h_ch5.appf.tab2_1_1_2_11 hd_h_ch5.appf.tab2_1_1_1_4 hd_h_ch5.appf.tab2_1_1_1_5" id="hd_b_ch5.appf.tab2_1_1_1_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:middle;">Change in creatinine (mmol/L; follow-up 12 months; Better indicated by lower values)</th></tr><tr><td headers="hd_h_ch5.appf.tab2_1_1_1_1 hd_h_ch5.appf.tab2_1_1_2_1 hd_b_ch5.appf.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch5.appf.tab2_1_1_1_1 hd_h_ch5.appf.tab2_1_1_2_2 hd_b_ch5.appf.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch5.appf.tab2_1_1_1_1 hd_h_ch5.appf.tab2_1_1_2_3 hd_b_ch5.appf.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious risk of bias</td><td headers="hd_h_ch5.appf.tab2_1_1_1_1 hd_h_ch5.appf.tab2_1_1_2_4 hd_b_ch5.appf.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch5.appf.tab2_1_1_1_1 hd_h_ch5.appf.tab2_1_1_2_5 hd_b_ch5.appf.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_ch5.appf.tab2_1_1_1_1 hd_h_ch5.appf.tab2_1_1_2_6 hd_b_ch5.appf.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious imprecision</td><td headers="hd_h_ch5.appf.tab2_1_1_1_1 hd_h_ch5.appf.tab2_1_1_2_7 hd_b_ch5.appf.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch5.appf.tab2_1_1_1_2 hd_h_ch5.appf.tab2_1_1_2_8 hd_b_ch5.appf.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">232</td><td headers="hd_h_ch5.appf.tab2_1_1_1_2 hd_h_ch5.appf.tab2_1_1_2_9 hd_b_ch5.appf.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">225</td><td headers="hd_h_ch5.appf.tab2_1_1_1_3 hd_h_ch5.appf.tab2_1_1_2_10 hd_b_ch5.appf.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-</td><td headers="hd_h_ch5.appf.tab2_1_1_1_3 hd_h_ch5.appf.tab2_1_1_2_11 hd_b_ch5.appf.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MD 2.3 higher (0.7 to 3.9 higher)</td><td headers="hd_h_ch5.appf.tab2_1_1_1_4 hd_b_ch5.appf.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>⨁⨁⨁⨁</p>
|
|
<p>HIGH</p>
|
|
</td><td headers="hd_h_ch5.appf.tab2_1_1_1_5 hd_b_ch5.appf.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch5.appf.tab2_1_1_1_1 hd_h_ch5.appf.tab2_1_1_2_1 hd_h_ch5.appf.tab2_1_1_2_2 hd_h_ch5.appf.tab2_1_1_2_3 hd_h_ch5.appf.tab2_1_1_2_4 hd_h_ch5.appf.tab2_1_1_2_5 hd_h_ch5.appf.tab2_1_1_2_6 hd_h_ch5.appf.tab2_1_1_2_7 hd_h_ch5.appf.tab2_1_1_1_2 hd_h_ch5.appf.tab2_1_1_2_8 hd_h_ch5.appf.tab2_1_1_2_9 hd_h_ch5.appf.tab2_1_1_1_3 hd_h_ch5.appf.tab2_1_1_2_10 hd_h_ch5.appf.tab2_1_1_2_11 hd_h_ch5.appf.tab2_1_1_1_4 hd_h_ch5.appf.tab2_1_1_1_5" id="hd_b_ch5.appf.tab2_1_1_3_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:middle;">Discontinuation due to adverse events (follow-up 12 months)</th></tr><tr><td headers="hd_h_ch5.appf.tab2_1_1_1_1 hd_h_ch5.appf.tab2_1_1_2_1 hd_b_ch5.appf.tab2_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch5.appf.tab2_1_1_1_1 hd_h_ch5.appf.tab2_1_1_2_2 hd_b_ch5.appf.tab2_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch5.appf.tab2_1_1_1_1 hd_h_ch5.appf.tab2_1_1_2_3 hd_b_ch5.appf.tab2_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>1</sup></td><td headers="hd_h_ch5.appf.tab2_1_1_1_1 hd_h_ch5.appf.tab2_1_1_2_4 hd_b_ch5.appf.tab2_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch5.appf.tab2_1_1_1_1 hd_h_ch5.appf.tab2_1_1_2_5 hd_b_ch5.appf.tab2_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_ch5.appf.tab2_1_1_1_1 hd_h_ch5.appf.tab2_1_1_2_6 hd_b_ch5.appf.tab2_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious<sup>2</sup></td><td headers="hd_h_ch5.appf.tab2_1_1_1_1 hd_h_ch5.appf.tab2_1_1_2_7 hd_b_ch5.appf.tab2_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch5.appf.tab2_1_1_1_2 hd_h_ch5.appf.tab2_1_1_2_8 hd_b_ch5.appf.tab2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
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<p>19/216</p>
|
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<p>(8.8%)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab2_1_1_1_2 hd_h_ch5.appf.tab2_1_1_2_9 hd_b_ch5.appf.tab2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>20/202</p>
|
|
<p>(9.9%)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab2_1_1_1_3 hd_h_ch5.appf.tab2_1_1_2_10 hd_b_ch5.appf.tab2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">RR 0.89 (0.49 to 1.62)</td><td headers="hd_h_ch5.appf.tab2_1_1_1_3 hd_h_ch5.appf.tab2_1_1_2_11 hd_b_ch5.appf.tab2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">11 fewer per 1000 (from 52 fewer to 58 more)</td><td headers="hd_h_ch5.appf.tab2_1_1_1_4 hd_b_ch5.appf.tab2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>VERY LOW</p>
|
|
</td><td headers="hd_h_ch5.appf.tab2_1_1_1_5 hd_b_ch5.appf.tab2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IMPORTANT</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1</dt><dd><div id="ch5.appf.tab2_1"><p class="no_margin">Downgraded by 1 increment if the majority of the evidence was at high risk of bias and downgraded by 2 increments if the majority of the evidence was at very high risk of bias</p></div></dd></dl><dl class="bkr_refwrap"><dt>2</dt><dd><div id="ch5.appf.tab2_2"><p class="no_margin">Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.</p></div></dd></dl></dl></div></div></div></article><article data-type="fig" id="figobch5appgfig1"><div id="ch5.appg.fig1" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%209.%20Flow%20chart%20of%20health%20economic%20study%20selection%20for%20the%20guideline.&p=BOOKS&id=578061_ch5appgf1.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK578061/bin/ch5appgf1.jpg" alt="Figure 9. Flow chart of health economic study selection for the guideline." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 9</span><span class="title">Flow chart of health economic study selection for the guideline</span></h3><div class="caption"><p>* Non-relevant population, intervention, comparison, design or setting; non-English language</p></div></div></article><article data-type="table-wrap" id="figobch5appitab1"><div id="ch5.appi.tab1" class="table"><h3><span class="label">Table 20</span><span class="title">Studies excluded from the clinical review</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.appi.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appi.tab1_lrgtbl__"><table><thead><tr><th id="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference</th><th id="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reason for exclusion</th></tr></thead><tbody><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Aalbers 2010<a class="bibr" href="#ch5.ref1" rid="ch5.ref1"><sup>1</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Abate 1998<a class="bibr" href="#ch5.ref2" rid="ch5.ref2"><sup>2</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Amir 1994<a class="bibr" href="#ch5.ref3" rid="ch5.ref3"><sup>3</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Anan 2005<a class="bibr" href="#ch5.ref4" rid="ch5.ref4"><sup>4</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Andersson 1999<a class="bibr" href="#ch5.ref5" rid="ch5.ref5"><sup>5</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Anderton 1988<a class="bibr" href="#ch5.ref6" rid="ch5.ref6"><sup>6</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No washout period</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Andreadis 2010<a class="bibr" href="#ch5.ref7" rid="ch5.ref7"><sup>7</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Andreadis 2005<a class="bibr" href="#ch5.ref8" rid="ch5.ref8"><sup>8</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Anonymous 1988<a class="bibr" href="#ch5.ref10" rid="ch5.ref10"><sup>10</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Anonymous (Veterans Administration cooperative study group) 1983<a class="bibr" href="#ch5.ref9" rid="ch5.ref9"><sup>9</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Aoki 1977<a class="bibr" href="#ch5.ref11" rid="ch5.ref11"><sup>11</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Applegate 1997<a class="bibr" href="#ch5.ref12" rid="ch5.ref12"><sup>12</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inappropriate washout period</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Bakris 2013<a class="bibr" href="#ch5.ref15" rid="ch5.ref15"><sup>15</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No washout period</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Basile 2011<a class="bibr" href="#ch5.ref16" rid="ch5.ref16"><sup>16</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Bays 2014<a class="bibr" href="#ch5.ref17" rid="ch5.ref17"><sup>17</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review; references checked</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Benedict group 2003<a class="bibr" href="#ch5.ref18" rid="ch5.ref18"><sup>18</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Benjamin 1988<a class="bibr" href="#ch5.ref19" rid="ch5.ref19"><sup>19</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Bennett 2017<a class="bibr" href="#ch5.ref20" rid="ch5.ref20"><sup>20</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review; references checked</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Beretta-Piccoli 1987<a class="bibr" href="#ch5.ref21" rid="ch5.ref21"><sup>21</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Bielmann 1991<a class="bibr" href="#ch5.ref22" rid="ch5.ref22"><sup>22</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Black 2008<a class="bibr" href="#ch5.ref23" rid="ch5.ref23"><sup>23</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect interventions</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Black 2002<a class="bibr" href="#ch5.ref24" rid="ch5.ref24"><sup>24</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Black 2003<a class="bibr" href="#ch5.ref25" rid="ch5.ref25"><sup>25</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect interventions</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Black 1998<a class="bibr" href="#ch5.ref26" rid="ch5.ref26"><sup>26</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study protocol</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Bohm 2017<a class="bibr" href="#ch5.ref28" rid="ch5.ref28"><sup>28</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect population</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Bomback 2012<a class="bibr" href="#ch5.ref29" rid="ch5.ref29"><sup>29</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Bradley 1975<a class="bibr" href="#ch5.ref30" rid="ch5.ref30"><sup>30</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Breithaupt-Grogler 1998<a class="bibr" href="#ch5.ref31" rid="ch5.ref31"><sup>31</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Bremner 1997<a class="bibr" href="#ch5.ref32" rid="ch5.ref32"><sup>32</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong comparison</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Bremner 1997<a class="bibr" href="#ch5.ref33" rid="ch5.ref33"><sup>33</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong comparison</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Brown 2015<a class="bibr" href="#ch5.ref38" rid="ch5.ref38"><sup>38</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Brown 2000<a class="bibr" href="#ch5.ref34" rid="ch5.ref34"><sup>34</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Brown 2001<a class="bibr" href="#ch5.ref35" rid="ch5.ref35"><sup>35</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Brown 1985<a class="bibr" href="#ch5.ref36" rid="ch5.ref36"><sup>36</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No relevant outcomes</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Brown 2008<a class="bibr" href="#ch5.ref37" rid="ch5.ref37"><sup>37</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Chalmers 1999<a class="bibr" href="#ch5.ref39" rid="ch5.ref39"><sup>39</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Chaugai 2018<a class="bibr" href="#ch5.ref40" rid="ch5.ref40"><sup>40</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong comparison</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Chung 2009<a class="bibr" href="#ch5.ref41" rid="ch5.ref41"><sup>41</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ciulla 2009<a class="bibr" href="#ch5.ref42" rid="ch5.ref42"><sup>42</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ciulla 2004<a class="bibr" href="#ch5.ref43" rid="ch5.ref43"><sup>43</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Cushman 1998<a class="bibr" href="#ch5.ref44" rid="ch5.ref44"><sup>44</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No useable outcomes</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dafgard 1981<a class="bibr" href="#ch5.ref45" rid="ch5.ref45"><sup>45</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No useable outcomes</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dahlof 2005<a class="bibr" href="#ch5.ref48" rid="ch5.ref48"><sup>48</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dahlof 1987<a class="bibr" href="#ch5.ref46" rid="ch5.ref46"><sup>46</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Damian 2016<a class="bibr" href="#ch5.ref49" rid="ch5.ref49"><sup>49</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong population</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">De Galan 2009<a class="bibr" href="#ch5.ref51" rid="ch5.ref51"><sup>51</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong comparison</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Degl’Innocenti 2004<a class="bibr" href="#ch5.ref53" rid="ch5.ref53"><sup>53</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong comparison</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Delea 2009<a class="bibr" href="#ch5.ref54" rid="ch5.ref54"><sup>54</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not article</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DeQuattro 1997<a class="bibr" href="#ch5.ref56" rid="ch5.ref56"><sup>56</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DeQuattro 1997<a class="bibr" href="#ch5.ref57" rid="ch5.ref57"><sup>57</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Derosa 2016<a class="bibr" href="#ch5.ref65" rid="ch5.ref65"><sup>65</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inappropriate washout period</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Derosa 2015<a class="bibr" href="#ch5.ref64" rid="ch5.ref64"><sup>64</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No relevant outcomes</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Derosa 2014<a class="bibr" href="#ch5.ref58" rid="ch5.ref58"><sup>58</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No useable outcomes</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Derosa 2013<a class="bibr" href="#ch5.ref59" rid="ch5.ref59"><sup>59</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Derosa 2013<a class="bibr" href="#ch5.ref60" rid="ch5.ref60"><sup>60</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inappropriate washout period</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Derosa 2014<a class="bibr" href="#ch5.ref62" rid="ch5.ref62"><sup>62</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inappropriate washout period</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Derosa 2013<a class="bibr" href="#ch5.ref61" rid="ch5.ref61"><sup>61</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Article retracted</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Derosa 2014<a class="bibr" href="#ch5.ref63" rid="ch5.ref63"><sup>63</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Article retracted</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Destro 2008<a class="bibr" href="#ch5.ref66" rid="ch5.ref66"><sup>66</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inappropriate washout period</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dickson 2008<a class="bibr" href="#ch5.ref67" rid="ch5.ref67"><sup>67</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Divitiis 1984<a class="bibr" href="#ch5.ref50" rid="ch5.ref50"><sup>50</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inappropriate washout period</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Drayer 1995<a class="bibr" href="#ch5.ref68" rid="ch5.ref68"><sup>68</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Duckett 1990<a class="bibr" href="#ch5.ref69" rid="ch5.ref69"><sup>69</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dzurik 1990<a class="bibr" href="#ch5.ref70" rid="ch5.ref70"><sup>70</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Elliot 1987<a class="bibr" href="#ch5.ref72" rid="ch5.ref72"><sup>72</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">El-Mehairy 1979<a class="bibr" href="#ch5.ref71" rid="ch5.ref71"><sup>71</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No useable outcomes</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Family Physicians Hypertension Study Group 1984<a class="bibr" href="#ch5.ref73" rid="ch5.ref73"><sup>73</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Fang 2014<a class="bibr" href="#ch5.ref74" rid="ch5.ref74"><sup>74</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No useable outcomes</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Feldman 2009<a class="bibr" href="#ch5.ref75" rid="ch5.ref75"><sup>75</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Fell 1990<a class="bibr" href="#ch5.ref76" rid="ch5.ref76"><sup>76</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ferrari 2008<a class="bibr" href="#ch5.ref77" rid="ch5.ref77"><sup>77</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review; references checked</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Fogari 2008<a class="bibr" href="#ch5.ref80" rid="ch5.ref80"><sup>80</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect washout period</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Fogari 2007<a class="bibr" href="#ch5.ref78" rid="ch5.ref78"><sup>78</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect comparison</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Fogari 2002<a class="bibr" href="#ch5.ref79" rid="ch5.ref79"><sup>79</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong population/inappropriate washout</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Forette 2002<a class="bibr" href="#ch5.ref81" rid="ch5.ref81"><sup>81</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong comparison</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Franklin 1996<a class="bibr" href="#ch5.ref82" rid="ch5.ref82"><sup>82</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Franz 1990<a class="bibr" href="#ch5.ref83" rid="ch5.ref83"><sup>83</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not in English</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Freytag 2002<a class="bibr" href="#ch5.ref84" rid="ch5.ref84"><sup>84</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Frishman 1995<a class="bibr" href="#ch5.ref85" rid="ch5.ref85"><sup>85</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Fu 2017<a class="bibr" href="#ch5.ref86" rid="ch5.ref86"><sup>86</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review; references checked</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Fujisaki 2014<a class="bibr" href="#ch5.ref87" rid="ch5.ref87"><sup>87</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Garcia de Vinuesa 2001<a class="bibr" href="#ch5.ref88" rid="ch5.ref88"><sup>88</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong population</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Garjon 2017<a class="bibr" href="#ch5.ref89" rid="ch5.ref89"><sup>89</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review; no relevant outcomes</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Girerd 1998<a class="bibr" href="#ch5.ref90" rid="ch5.ref90"><sup>90</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Goodman 1985<a class="bibr" href="#ch5.ref91" rid="ch5.ref91"><sup>91</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Goyal 2014<a class="bibr" href="#ch5.ref92" rid="ch5.ref92"><sup>92</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Grassi 2010<a class="bibr" href="#ch5.ref93" rid="ch5.ref93"><sup>93</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review; references checked</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Grimm 1996<a class="bibr" href="#ch5.ref94" rid="ch5.ref94"><sup>94</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Gupta 2008<a class="bibr" href="#ch5.ref95" rid="ch5.ref95"><sup>95</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Guyot 1990<a class="bibr" href="#ch5.ref96" rid="ch5.ref96"><sup>96</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not in English</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hall 1998<a class="bibr" href="#ch5.ref98" rid="ch5.ref98"><sup>98</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hall 1998<a class="bibr" href="#ch5.ref97" rid="ch5.ref97"><sup>97</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Harmankaya 2003<a class="bibr" href="#ch5.ref99" rid="ch5.ref99"><sup>99</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No useable outcomes, less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hasegawa 2004<a class="bibr" href="#ch5.ref100" rid="ch5.ref100"><sup>100</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong population</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">He 2017<a class="bibr" href="#ch5.ref101" rid="ch5.ref101"><sup>101</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review; references checked</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Heidbreder 1992<a class="bibr" href="#ch5.ref103" rid="ch5.ref103"><sup>103</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inappropriate washout period, less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Heidbreder 1991<a class="bibr" href="#ch5.ref102" rid="ch5.ref102"><sup>102</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong population</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Helmer 2018<a class="bibr" href="#ch5.ref104" rid="ch5.ref104"><sup>104</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review; references checked</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Herlitz 2001<a class="bibr" href="#ch5.ref105" rid="ch5.ref105"><sup>105</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong comparison</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hersh 1995<a class="bibr" href="#ch5.ref106" rid="ch5.ref106"><sup>106</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hill 1985<a class="bibr" href="#ch5.ref107" rid="ch5.ref107"><sup>107</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration, incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hilleman 1999<a class="bibr" href="#ch5.ref108" rid="ch5.ref108"><sup>108</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review; references checked</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hofling 1991<a class="bibr" href="#ch5.ref109" rid="ch5.ref109"><sup>109</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not in English</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Holzgreve 1989<a class="bibr" href="#ch5.ref111" rid="ch5.ref111"><sup>111</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong population</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Holzgreve 2003<a class="bibr" href="#ch5.ref110" rid="ch5.ref110"><sup>110</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not article</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Home 2009<a class="bibr" href="#ch5.ref112" rid="ch5.ref112"><sup>112</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong population/interventions</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ihm 2016<a class="bibr" href="#ch5.ref113" rid="ch5.ref113"><sup>113</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ishimitsu 1997<a class="bibr" href="#ch5.ref114" rid="ch5.ref114"><sup>114</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Jang 2015<a class="bibr" href="#ch5.ref115" rid="ch5.ref115"><sup>115</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Jicheng 2009<a class="bibr" href="#ch5.ref135" rid="ch5.ref135"><sup>135</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong interventions</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Johnson 1994<a class="bibr" href="#ch5.ref117" rid="ch5.ref117"><sup>117</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design; no relevant outcomes</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Johnson 2005<a class="bibr" href="#ch5.ref116" rid="ch5.ref116"><sup>116</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong study design, wrong population</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Katayama 2006<a class="bibr" href="#ch5.ref118" rid="ch5.ref118"><sup>118</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Kim 2011<a class="bibr" href="#ch5.ref122" rid="ch5.ref122"><sup>122</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Kim 2014<a class="bibr" href="#ch5.ref120" rid="ch5.ref120"><sup>120</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong population</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Kim 2016<a class="bibr" href="#ch5.ref121" rid="ch5.ref121"><sup>121</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong population, less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Kinouchi 2011<a class="bibr" href="#ch5.ref123" rid="ch5.ref123"><sup>123</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No useable outcomes</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Kjeldsen 2016<a class="bibr" href="#ch5.ref124" rid="ch5.ref124"><sup>124</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Kjeldsen 2008<a class="bibr" href="#ch5.ref126" rid="ch5.ref126"><sup>126</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong comparison</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Kjeldsen 2002<a class="bibr" href="#ch5.ref125" rid="ch5.ref125"><sup>125</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Kostis 2004<a class="bibr" href="#ch5.ref128" rid="ch5.ref128"><sup>128</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Abstract</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Kostis 1997<a class="bibr" href="#ch5.ref127" rid="ch5.ref127"><sup>127</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong population</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Kuschnir 2004<a class="bibr" href="#ch5.ref129" rid="ch5.ref129"><sup>129</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration, inappropriate washout</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Lassila 2000<a class="bibr" href="#ch5.ref130" rid="ch5.ref130"><sup>130</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong population/wrong interventions</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Laurent 2001<a class="bibr" href="#ch5.ref131" rid="ch5.ref131"><sup>131</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Literature review</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Li 2014<a class="bibr" href="#ch5.ref132" rid="ch5.ref132"><sup>132</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect population</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Lucas 1985<a class="bibr" href="#ch5.ref134" rid="ch5.ref134"><sup>134</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MacDonald 2015<a class="bibr" href="#ch5.ref136" rid="ch5.ref136"><sup>136</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MacKay 1996<a class="bibr" href="#ch5.ref137" rid="ch5.ref137"><sup>137</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Malacco 2008<a class="bibr" href="#ch5.ref138" rid="ch5.ref138"><sup>138</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mancia 2017<a class="bibr" href="#ch5.ref140" rid="ch5.ref140"><sup>140</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Subgroup analysis</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mancia 2012<a class="bibr" href="#ch5.ref141" rid="ch5.ref141"><sup>141</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong population</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Marques da Silva 2015<a class="bibr" href="#ch5.ref142" rid="ch5.ref142"><sup>142</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect comparison</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Masao 1994<a class="bibr" href="#ch5.ref143" rid="ch5.ref143"><sup>143</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not in English</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Matsuzaki 2011<a class="bibr" href="#ch5.ref144" rid="ch5.ref144"><sup>144</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong comparison</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mayaudon 1995<a class="bibr" href="#ch5.ref145" rid="ch5.ref145"><sup>145</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not in English</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Miyoshi 2017<a class="bibr" href="#ch5.ref147" rid="ch5.ref147"><sup>147</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Morgan 2002<a class="bibr" href="#ch5.ref149" rid="ch5.ref149"><sup>149</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inappropriate washout period</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Morgan 2004<a class="bibr" href="#ch5.ref150" rid="ch5.ref150"><sup>150</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MRC Working Party 1992<a class="bibr" href="#ch5.ref151" rid="ch5.ref151"><sup>151</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Nakao 2004<a class="bibr" href="#ch5.ref152" rid="ch5.ref152"><sup>152</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Nalbantgil 2003<a class="bibr" href="#ch5.ref153" rid="ch5.ref153"><sup>153</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Nedogoda 2005<a class="bibr" href="#ch5.ref156" rid="ch5.ref156"><sup>156</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not in English</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Neldam 2012<a class="bibr" href="#ch5.ref157" rid="ch5.ref157"><sup>157</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review; references checked</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Neldam 2012<a class="bibr" href="#ch5.ref158" rid="ch5.ref158"><sup>158</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review; references checked</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Nelson 1982<a class="bibr" href="#ch5.ref159" rid="ch5.ref159"><sup>159</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Neutel 2000<a class="bibr" href="#ch5.ref162" rid="ch5.ref162"><sup>162</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Neutel 1999<a class="bibr" href="#ch5.ref161" rid="ch5.ref161"><sup>161</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration. Wrong population</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Neutel 2014<a class="bibr" href="#ch5.ref160" rid="ch5.ref160"><sup>160</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Obel 1990<a class="bibr" href="#ch5.ref163" rid="ch5.ref163"><sup>163</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Olivan Martinez 1993<a class="bibr" href="#ch5.ref164" rid="ch5.ref164"><sup>164</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not in English</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Packer 2013<a class="bibr" href="#ch5.ref165" rid="ch5.ref165"><sup>165</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong population</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Pannier 2002<a class="bibr" href="#ch5.ref166" rid="ch5.ref166"><sup>166</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not in English</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Papademetriou 2009<a class="bibr" href="#ch5.ref167" rid="ch5.ref167"><sup>167</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Papademetriou 1998<a class="bibr" href="#ch5.ref168" rid="ch5.ref168"><sup>168</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Park 2016<a class="bibr" href="#ch5.ref171" rid="ch5.ref171"><sup>171</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Park 2016<a class="bibr" href="#ch5.ref169" rid="ch5.ref169"><sup>169</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong population, less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Park 2016<a class="bibr" href="#ch5.ref170" rid="ch5.ref170"><sup>170</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect population</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Patel 2007<a class="bibr" href="#ch5.ref172" rid="ch5.ref172"><sup>172</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design, less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Paz 2016<a class="bibr" href="#ch5.ref173" rid="ch5.ref173"><sup>173</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review; references checked</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Perez-Maraver 2005<a class="bibr" href="#ch5.ref174" rid="ch5.ref174"><sup>174</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong population</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Persson 1976<a class="bibr" href="#ch5.ref175" rid="ch5.ref175"><sup>175</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Pessina 2006<a class="bibr" href="#ch5.ref176" rid="ch5.ref176"><sup>176</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Petelina 2005<a class="bibr" href="#ch5.ref177" rid="ch5.ref177"><sup>177</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not in English</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Petersen 2001<a class="bibr" href="#ch5.ref178" rid="ch5.ref178"><sup>178</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong population</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Petrie 1975<a class="bibr" href="#ch5.ref179" rid="ch5.ref179"><sup>179</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inappropriate washout period, less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Pool 2009<a class="bibr" href="#ch5.ref180" rid="ch5.ref180"><sup>180</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Prisant 1998<a class="bibr" href="#ch5.ref181" rid="ch5.ref181"><sup>181</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Radevski 2000<a class="bibr" href="#ch5.ref183" rid="ch5.ref183"><sup>183</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong population</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Radevski 1999<a class="bibr" href="#ch5.ref182" rid="ch5.ref182"><sup>182</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong comparison</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Rakesh 2017<a class="bibr" href="#ch5.ref184" rid="ch5.ref184"><sup>184</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No useable outcomes</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ratnasabapathy 2003<a class="bibr" href="#ch5.ref185" rid="ch5.ref185"><sup>185</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong comparison</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Redon 2012<a class="bibr" href="#ch5.ref186" rid="ch5.ref186"><sup>186</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong comparison</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Roca-Cusachs 2001<a class="bibr" href="#ch5.ref187" rid="ch5.ref187"><sup>187</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Rosenfeld 1989<a class="bibr" href="#ch5.ref188" rid="ch5.ref188"><sup>188</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ruggenenti 2011<a class="bibr" href="#ch5.ref191" rid="ch5.ref191"><sup>191</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ruggenenti 2004<a class="bibr" href="#ch5.ref190" rid="ch5.ref190"><sup>190</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong population</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ruggenenti 2011<a class="bibr" href="#ch5.ref189" rid="ch5.ref189"><sup>189</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Saruta 2015<a class="bibr" href="#ch5.ref193" rid="ch5.ref193"><sup>193</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong comparison</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sassano 1989<a class="bibr" href="#ch5.ref194" rid="ch5.ref194"><sup>194</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Seedat 1984<a class="bibr" href="#ch5.ref196" rid="ch5.ref196"><sup>196</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Seedat 1983<a class="bibr" href="#ch5.ref195" rid="ch5.ref195"><sup>195</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Shaifali 2014<a class="bibr" href="#ch5.ref197" rid="ch5.ref197"><sup>197</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No useable outcomes</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Shi 2017<a class="bibr" href="#ch5.ref198" rid="ch5.ref198"><sup>198</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No relevant outcomes</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Shimamoto 2015<a class="bibr" href="#ch5.ref199" rid="ch5.ref199"><sup>199</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inappropriate washout period</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Smith 2007<a class="bibr" href="#ch5.ref200" rid="ch5.ref200"><sup>200</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sohn 2017<a class="bibr" href="#ch5.ref201" rid="ch5.ref201"><sup>201</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Soucek 2007<a class="bibr" href="#ch5.ref202" rid="ch5.ref202"><sup>202</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not in English</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sung 2016<a class="bibr" href="#ch5.ref203" rid="ch5.ref203"><sup>203</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Thijs 2010<a class="bibr" href="#ch5.ref205" rid="ch5.ref205"><sup>205</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Timofeeva 2006<a class="bibr" href="#ch5.ref206" rid="ch5.ref206"><sup>206</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not in English</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Umemoto 2017<a class="bibr" href="#ch5.ref208" rid="ch5.ref208"><sup>208</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Subgroup analysis</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Umemoto 2016<a class="bibr" href="#ch5.ref207" rid="ch5.ref207"><sup>207</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Subgroup analysis</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Uzui 2014<a class="bibr" href="#ch5.ref209" rid="ch5.ref209"><sup>209</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong comparison</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wang 2017<a class="bibr" href="#ch5.ref210" rid="ch5.ref210"><sup>210</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Weinberger 1982<a class="bibr" href="#ch5.ref211" rid="ch5.ref211"><sup>211</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Weir 2001<a class="bibr" href="#ch5.ref212" rid="ch5.ref212"><sup>212</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">White 1995<a class="bibr" href="#ch5.ref213" rid="ch5.ref213"><sup>213</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wilhelmsen 1987<a class="bibr" href="#ch5.ref214" rid="ch5.ref214"><sup>214</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Yip 2008<a class="bibr" href="#ch5.ref216" rid="ch5.ref216"><sup>216</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Yu 2011<a class="bibr" href="#ch5.ref217" rid="ch5.ref217"><sup>217</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not in English</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Yusuf 2016<a class="bibr" href="#ch5.ref218" rid="ch5.ref218"><sup>218</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong comparison</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Yusuf 2008<a class="bibr" href="#ch5.ref219" rid="ch5.ref219"><sup>219</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong population</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Zanchetti 2006<a class="bibr" href="#ch5.ref220" rid="ch5.ref220"><sup>220</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Literature review</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Zhang 2010<a class="bibr" href="#ch5.ref221" rid="ch5.ref221"><sup>221</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inappropriate washout</td></tr><tr><td headers="hd_h_ch5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Zhu 2013<a class="bibr" href="#ch5.ref222" rid="ch5.ref222"><sup>222</sup></a></td><td headers="hd_h_ch5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Less than minimum duration</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5appitab2"><div id="ch5.appi.tab2" class="table"><h3><span class="label">Table 21</span><span class="title">Studies excluded from the health economic review</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.appi.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appi.tab2_lrgtbl__"><table><thead><tr><th id="hd_h_ch5.appi.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference</th><th id="hd_h_ch5.appi.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reason for exclusion</th></tr></thead><tbody><tr><td headers="hd_h_ch5.appi.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Kato 2015<a class="bibr" href="#ch5.ref119" rid="ch5.ref119"><sup>119</sup></a></td><td headers="hd_h_ch5.appi.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">This study was assessed as partially applicable with very serious limitations because it was a before-and-after study comparing whether switching from monotherapy to combination therapy is cost effective. Clinical data does not meet the requirements of clinical review.</td></tr><tr><td headers="hd_h_ch5.appi.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mazza 2017<a class="bibr" href="#ch5.ref146" rid="ch5.ref146"><sup>146</sup></a></td><td headers="hd_h_ch5.appi.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">This study was assessed as partially applicable with very serious limitations because it is based on retrospective data, and blood pressure lowering is used for effect rather than clinical endpoints. Therefore, clinical data does not meet the requirements of clinical review.</td></tr><tr><td headers="hd_h_ch5.appi.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Saito 2008<a class="bibr" href="#ch5.ref192" rid="ch5.ref192"><sup>192</sup></a></td><td headers="hd_h_ch5.appi.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">This study was assessed as partially applicable with very serious limitations because the effectiveness of the combination treatment is based on an assumption (assumption of on-treatment blood pressure) rather than being based on a clinical trial. This also seems to have been put through a risk calculator, which should ideally be used for baseline risks rather than risks post treatment. Therefore, clinical data does not meet the requirements of clinical review.</td></tr><tr><td headers="hd_h_ch5.appi.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wisloff 2012<a class="bibr" href="#ch5.ref215" rid="ch5.ref215"><sup>215</sup></a></td><td headers="hd_h_ch5.appi.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">This study was assessed as partially applicable with very serious limitations because the effectiveness of the combination treatment is multiplicative rather than being based on a clinical trial. Therefore, clinical data does not meet the requirements of clinical review.</td></tr><tr><td headers="hd_h_ch5.appi.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Szucs 2010<a class="bibr" href="#ch5.ref204" rid="ch5.ref204"><sup>204</sup></a></td><td headers="hd_h_ch5.appi.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">This was a study included in the previous guideline. This study was assessed as not applicable because treatment is being compared to no treatment.</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5appjtab1"><div id="ch5.appj.tab1" class="table"><h3><span class="title">Criteria for selecting high-priority research recommendations</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK578061/table/ch5.appj.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appj.tab1_lrgtbl__"><table><tbody><tr><th id="hd_b_ch5.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">PICO question</th><td headers="hd_b_ch5.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Population: Adults (over the age of 18) who meet the criteria for medication to be initiated for the treatment of hypertension, split into subgroups including type 2 diabetes, history of stroke, history of cardiovascular disease, or pre-existing CKD.</p>
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<p>Intervention(s): Dual therapy as an initial treatment strategy in the treatment of hypertension.</p>
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<p>Comparison: Single agent therapy.</p>
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<p>Outcome(s): Critical: All-cause mortality, stroke (ischaemic or haemorrhagic), myocardial infarction, health related quality of life, and development or progression of chronic kidney disease (CKD). Important: Time to reach blood pressure target,</p>
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</td></tr><tr><th id="hd_b_ch5.appj.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Importance to patients or the population</th><td headers="hd_b_ch5.appj.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Impact would be delay in the development of or slowing the progression of adverse outcomes without an increase in adverse events as a result of the treatment regimen.</td></tr><tr><th id="hd_b_ch5.appj.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Relevance to NICE guidance</th><td headers="hd_b_ch5.appj.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">This would impact the recommendations within the NICE clinical guideline for hypertension as to whether staged treatment (as per current guideline) is retained or whether dual therapy would be recommended for any specific subgroups of people.</td></tr><tr><th id="hd_b_ch5.appj.tab1_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Relevance to the NHS</th><td headers="hd_b_ch5.appj.tab1_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>If blood pressure targets are attained in a more timely fashion without additional adverse effects, this may be cost effective in terms of number of clinic appointments or consultations required.</p>
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<p>If improved cardiovascular outcomes, this would be cost effective and would reduce the QALY associated with treatment of hypertension.</p>
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</td></tr><tr><th id="hd_b_ch5.appj.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">National priorities</th><td headers="hd_b_ch5.appj.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N/A</td></tr><tr><th id="hd_b_ch5.appj.tab1_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Current evidence base</th><td headers="hd_b_ch5.appj.tab1_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Although there was some evidence identified for using dual therapy, this was not in hard clinical outcomes and therefore further evidence with these outcomes could inform future updates of the guideline.</td></tr><tr><th id="hd_b_ch5.appj.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Equality</th><td headers="hd_b_ch5.appj.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">There are no expected equality issues.</td></tr><tr><th id="hd_b_ch5.appj.tab1_1_1_8_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study design</th><td headers="hd_b_ch5.appj.tab1_1_1_8_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">This question would be best answered by an RCT although the duration of follow up required means that a long-term (at least 5 years) study would be required.</td></tr><tr><th id="hd_b_ch5.appj.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Feasibility</th><td headers="hd_b_ch5.appj.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The study would need a 5-year follow-up. Technically, it should be straight forward, but funding could be an issue.</td></tr><tr><th id="hd_b_ch5.appj.tab1_1_1_10_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Other comments</th><td headers="hd_b_ch5.appj.tab1_1_1_10_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">As the medications used for the treatment of hypertension are generic, it is unlikely that any funding would be forthcoming from the pharmaceutical industry, so the research would need to be funded by a central body.</td></tr><tr><th id="hd_b_ch5.appj.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Importance</th><td headers="hd_b_ch5.appj.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Medium: the research is relevant to the recommendations in the guideline, but the research recommendations are not key to future updates.</td></tr></tbody></table></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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