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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Clopidogrel Therapy and CYP2C19 Genotype - Medical Genetics Summaries - NCBI Bookshelf</title>
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<meta name="citation_keywords" content="clopidogrel resistance">
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match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK84114_"><span class="title" itemprop="name">Clopidogrel Therapy and <i>CYP2C19</i> Genotype</span></h1><p class="contribs">Dean L, Kane M.</p><p class="fm-aai"><a href="#_NBK84114_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 29 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="clopidogrel.Introduction" itemprop="description"><h2 id="_clopidogrel_Introduction_">Introduction</h2><p>Clopidogrel (brand name Plavix) is an antiplatelet medicine that reduces the risk of myocardial infarction (MI) and stroke in individuals with acute coronary syndrome (ACS), and in individuals with atherosclerotic vascular disease (indicated by a recent MI or stroke, or established peripheral arterial disease) (<a class="bibr" href="#clopidogrel.REF.1" rid="clopidogrel.REF.1">1</a>). Clopidogrel is also indicated in combination with aspirin for individuals undergoing percutaneous coronary interventions (PCI), including stent placement.</p><p>The effectiveness of clopidogrel depends on its conversion to an active metabolite, which is accomplished by the cytochrome P450 2C19 (CYP2C19) enzyme. Individuals who have 2 loss-of-function copies of the <i>CYP2C19</i> gene are classified as CYP2C19 poor metabolizers (PM). Individuals with a CYP2C19 PM phenotype have significantly reduced enzyme activity and cannot activate clopidogrel via CYP2C19, which means the drug will have a reduced antiplatelet effect. Approximately 2% of Caucasians, 4% of African Americans, 14% of Chinese, and 57% of Oceanians are CYP2C19 PMs (<a class="bibr" href="#clopidogrel.REF.2" rid="clopidogrel.REF.2">2</a>). The effectiveness of clopidogrel is also reduced in individuals who are CYP2C19 intermediate metabolizers (IM). These individuals have one loss-of-function copy of <i>CYP2C19</i>, with either one normal function copy or one increased function copy. The frequency of the IM phenotype is more than 45% in individuals of East Asian descent, more than 40% in individuals of Central or South Asian descent, 36% in the Oceanian population, approximately 30% in individuals of African descent, 20–26% in individuals of American, European, or Near Eastern descent, and just under 20% in individuals of Latino descent (<a class="bibr" href="#clopidogrel.REF.2" rid="clopidogrel.REF.2">2</a>).</p><p>The 2022 FDA-approved drug label for clopidogrel includes a boxed warning on the diminished antiplatelet effect of clopidogrel in CYP2C19 PMs (<a href="/books/NBK84114/table/clopidogrel.T.the_fda_2022_drug_label_fo/?report=objectonly" target="object" rid-ob="figobclopidogrelTthefda2022druglabelfo">Table 1</a>). The warning states that tests are available to identify individuals who are CYP2C19 PMs, and to consider the use of another platelet P2Y<sub>12</sub> (purinergic receptor P2Y, G-protein coupled 12) inhibitor in individuals identified as CYP2C19 PMs.</p><p>The 2022 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for clopidogrel recommends that for individuals with ACS or non-ACS indications who are undergoing PCI, being treated for peripheral arterial disease (PAD), or stable coronary artery disease following MI, an alternative antiplatelet therapy (for example, prasugrel or ticagrelor) should be considered for CYP2C19 PMs if there is no contraindication (<a href="/books/NBK84114/table/clopidogrel.T.the_cpic_2022_antiplatelet/?report=objectonly" target="object" rid-ob="figobclopidogrelTthecpic2022antiplatelet">Table 2</a>) (<a class="bibr" href="#clopidogrel.REF.3" rid="clopidogrel.REF.3">3</a>). Similarly, CPIC strongly recommends that CYP2C19 IMs should avoid clopidogrel for ACS or PCI but makes no recommendations for other cardiovascular indications (<a href="/books/NBK84114/table/clopidogrel.T.the_cpic_2022_antiplatelet/?report=objectonly" target="object" rid-ob="figobclopidogrelTthecpic2022antiplatelet">Table 2</a>). For neurovascular indications, CPIC recommends avoidance of clopidogrel for CYP2C19 PMs and consideration of alternative medications for both IMs and PMs if not contraindicated (<a href="/books/NBK84114/table/clopidogrel.T.the_cpic_2022_antiplatelet_1/?report=objectonly" target="object" rid-ob="figobclopidogrelTthecpic2022antiplatelet1">Table 3</a>) (<a class="bibr" href="#clopidogrel.REF.3" rid="clopidogrel.REF.3">3</a>).</p><p>The Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Association for the Advancement of Pharmacy (KNMP) have also made antiplatelet therapy recommendations based on <i>CYP2C19</i> genotype. For individuals with ACS who undergo PCI, they recommend an alternative antiplatelet agent in PMs, and for IMs they recommend choosing an alternative antiplatelet agent or doubling the dose of clopidogrel to 150 mg daily dose, 600 mg loading dose (<a href="/books/NBK84114/table/clopidogrel.T.the_dpwg_2019_recommendati/?report=objectonly" target="object" rid-ob="figobclopidogrelTthedpwg2019recommendati">Table 4</a>) (<a class="bibr" href="#clopidogrel.REF.4" rid="clopidogrel.REF.4">4</a>).</p></div><div class="h2"></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figclopidogrelTthefda2022druglabelfo"><a href="/books/NBK84114/table/clopidogrel.T.the_fda_2022_drug_label_fo/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobclopidogrelTthefda2022druglabelfo"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="clopidogrel.T.the_fda_2022_drug_label_fo"><a href="/books/NBK84114/table/clopidogrel.T.the_fda_2022_drug_label_fo/?report=objectonly" target="object" rid-ob="figobclopidogrelTthefda2022druglabelfo">Table 1. </a></h4><p class="float-caption no_bottom_margin">The FDA (2022) Drug Label for Clopidogrel. Warning: Diminished Antiplatelet Effect in Individuals with 2 Loss-of-Function Alleles of the <i>CYP2C19</i> Gene. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figclopidogrelTthecpic2022antiplatelet"><a href="/books/NBK84114/table/clopidogrel.T.the_cpic_2022_antiplatelet/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobclopidogrelTthecpic2022antiplatelet"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="clopidogrel.T.the_cpic_2022_antiplatelet"><a href="/books/NBK84114/table/clopidogrel.T.the_cpic_2022_antiplatelet/?report=objectonly" target="object" rid-ob="figobclopidogrelTthecpic2022antiplatelet">Table 2. </a></h4><p class="float-caption no_bottom_margin">The CPIC (2022) Antiplatelet Therapy Recommendations based on CYP2C19 Phenotype when considering Clopidogrel for Cardiovascular Indications. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figclopidogrelTthecpic2022antiplatelet1"><a href="/books/NBK84114/table/clopidogrel.T.the_cpic_2022_antiplatelet_1/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobclopidogrelTthecpic2022antiplatelet1"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="clopidogrel.T.the_cpic_2022_antiplatelet_1"><a href="/books/NBK84114/table/clopidogrel.T.the_cpic_2022_antiplatelet_1/?report=objectonly" target="object" rid-ob="figobclopidogrelTthecpic2022antiplatelet1">Table 3. </a></h4><p class="float-caption no_bottom_margin">The CPIC (2022) Antiplatelet Therapy Recommendations Based on CYP2C19 Phenotype when Considering Clopidogrel for Neurovascular<sup>a</sup> Indications </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figclopidogrelTthedpwg2019recommendati"><a href="/books/NBK84114/table/clopidogrel.T.the_dpwg_2019_recommendati/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobclopidogrelTthedpwg2019recommendati"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="clopidogrel.T.the_dpwg_2019_recommendati"><a href="/books/NBK84114/table/clopidogrel.T.the_dpwg_2019_recommendati/?report=objectonly" target="object" rid-ob="figobclopidogrelTthedpwg2019recommendati">Table 4. </a></h4><p class="float-caption no_bottom_margin">The DPWG (2019) Recommendations for Clopidogrel and <i>CYP2C19</i> Phenotype. </p></div></div><div id="clopidogrel.Drug_Clopidogrel"><h2 id="_clopidogrel_Drug_Clopidogrel_">Drug: Clopidogrel</h2><p>Clopidogrel is an antiplatelet medicine used in the treatment of individuals with ACS, managed medically or with PCI. Clopidogrel is also used in the treatment of individuals with atherosclerotic vascular disease, as indicated by a recent MI, a recent ischemic stroke, or symptomatic peripheral arterial disease. Clopidogrel has been shown to reduce the rate of subsequent MI and stroke in these individuals (<a class="bibr" href="#clopidogrel.REF.1" rid="clopidogrel.REF.1">1</a>, <a class="bibr" href="#clopidogrel.REF.5" rid="clopidogrel.REF.5">5</a>, <a class="bibr" href="#clopidogrel.REF.6" rid="clopidogrel.REF.6">6</a>).</p><p>Clopidogrel is a P2Y<sub>12</sub> inhibitor, and acts by irreversibly binding to the platelet P2Y<sub>12</sub> receptor and blocking adenosine diphosphate (ADP)-mediated platelet activation and aggregation. Clopidogrel belongs to the second generation of thienopyridine antiplatelet agents.</p><p>Clopidogrel is given to treat or to prevent further occurrences of arterial thrombosis, which occurs when a blood clot (thrombus) forms inside an artery. Arterial thrombosis is often triggered in response to the rupturing of the atherosclerotic plaque lining the arterial wall. If the thrombus occludes the arterial lumen, the blood flow is reduced or stopped, resulting in ischemia. In the brain, thrombosis in the cerebral arteries can cause a transient ischemic attack (TIA) or ischemic stroke. In the peripheral vessels, thrombosis can cause peripheral artery disease, and in the heart, a thrombosis in the coronary arteries is a common cause of ACS. Platelet inhibitors such as clopidogrel interrupt the formation of the thrombus, which involves the rapid recruitment and activation of platelets.</p><p>Acute coronary syndrome reflects a decreased blood flow in the coronary arteries and comprises unstable angina and MI. Unstable angina occurs suddenly, often at rest or with minimal exertion, and may be new in onset or may occur with less exertion than previously.</p><p>Among individuals with ACS, the addition of 75 mg daily clopidogrel to aspirin and other standard treatments reduces the risk of MI, stroke, and death, compared with the addition of placebo (<a class="bibr" href="#clopidogrel.REF.7" rid="clopidogrel.REF.7">7</a>, <a class="bibr" href="#clopidogrel.REF.8" rid="clopidogrel.REF.8">8</a>, <a class="bibr" href="#clopidogrel.REF.9" rid="clopidogrel.REF.9">9</a>). However, despite the general efficacy of clopidogrel, resistance is common. Resistance to an antiplatelet drug occurs when there is no significant reduction in platelet function after therapy, compared with baseline platelet function. Clopidogrel treatment failure occurs when there is a thrombotic or ischemic event (for example, stent thrombosis or recurrent ACS) during clopidogrel therapy in individuals with “High on-Treatment Platelet Reactivity” (HTPR). High on-Treatment Platelet Reactivity occurs when the platelet P2Y<sub>12</sub> receptors are still responsive despite clopidogrel therapy. It is tested for by adding an ADP agonist to a plasma sample and measuring aggregation or intracellular markers of platelet activation. It has been estimated that between 16–50% of individuals treated with clopidogrel have HTPR (<a class="bibr" href="#clopidogrel.REF.10" rid="clopidogrel.REF.10">10</a>).</p><p>Platelet function assays are used to assess platelet response by measuring ‘Platelet Reactivity Units’ (PRU). The PRU cut-off values vary, but the therapeutic window for clopidogrel is approximately 95–208 PRU. A PRU value higher than 208 indicates clopidogrel resistance, and a value below 95 is associated with a higher risk for major bleeding (<a class="bibr" href="#clopidogrel.REF.11" rid="clopidogrel.REF.11">11</a>, <a class="bibr" href="#clopidogrel.REF.12" rid="clopidogrel.REF.12">12</a>). Many studies have reported an association between clopidogrel resistance (HTPR or high PRU) and an increased risk of thrombotic/ischemic event following PCI, such as stent thrombosis (<a class="bibr" href="#clopidogrel.REF.13" rid="clopidogrel.REF.13">13</a>). Similarly, HTPR is associated with poor outcomes in stroke or TIA in the context of standard antiplatelet therapies, including clopidogrel (<a class="bibr" href="#clopidogrel.REF.14" rid="clopidogrel.REF.14">14</a>).</p><p>A poor response to clopidogrel is due, in part, to genetic variants in the <i>CYP2C19</i> gene. Other genes that may influence clopidogrel response include <i>ABCB1</i>, <i>P2Y12</i>, <i>CES1</i>, <i>GPIIIA</i>, <i>B4GALT2,</i> and <i>PON1</i> (<a class="bibr" href="#clopidogrel.REF.15" rid="clopidogrel.REF.15">15</a>, <a class="bibr" href="#clopidogrel.REF.16" rid="clopidogrel.REF.16">16</a>, <a class="bibr" href="#clopidogrel.REF.17" rid="clopidogrel.REF.17">17</a>, <a class="bibr" href="#clopidogrel.REF.18" rid="clopidogrel.REF.18">18</a>, <a class="bibr" href="#clopidogrel.REF.19" rid="clopidogrel.REF.19">19</a>, <a class="bibr" href="#clopidogrel.REF.20" rid="clopidogrel.REF.20">20</a>, <a class="bibr" href="#clopidogrel.REF.21" rid="clopidogrel.REF.21">21</a>, <a class="bibr" href="#clopidogrel.REF.22" rid="clopidogrel.REF.22">22</a>, <a class="bibr" href="#clopidogrel.REF.23" rid="clopidogrel.REF.23">23</a>). Clopidogrel is a prodrug, and CYP2C19 is the major enzyme involved in the conversion of clopidogrel into an active metabolite. Alternative antiplatelet drugs to clopidogrel, such as <a href="/books/n/gtrbook/prasugrel/?report=reader">prasugrel</a> (a third generation thienopyridine) and ticagrelor (a cyclopentyltriazolopyrimidine), are not dependent upon CYP2C19 for activation. Although both clopidogrel and prasugrel form active metabolites with similar potency, prasugrel is a more potent antiplatelet agent than clopidogrel due to the more efficient formation of the active metabolite from the prodrug (<a class="bibr" href="#clopidogrel.REF.24" rid="clopidogrel.REF.24">24</a>).</p><p>The TRITON-TIMI 38 trial compared prasugrel with clopidogrel in 13,608 individuals with ACS who were undergoing PCI. Prasugrel was found to provide more potent platelet inhibition than clopidogrel; and after 15 months, individuals treated with prasugrel had a lower incidence of the combined endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke as compared with individuals treated with clopidogrel (9.9% versus 12.1%) (<a class="bibr" href="#clopidogrel.REF.25" rid="clopidogrel.REF.25">25</a>, <a class="bibr" href="#clopidogrel.REF.26" rid="clopidogrel.REF.26">26</a>). However, prasugrel was associated with a higher risk of bleeding, leading to the FDA warning that the use of prasugrel is contraindicated in individuals with active pathological bleeding, or a history of stroke or TIA (<a class="bibr" href="#clopidogrel.REF.27" rid="clopidogrel.REF.27">27</a>, <a class="bibr" href="#clopidogrel.REF.28" rid="clopidogrel.REF.28">28</a>). In addition, prasugrel has an FDA box warning for individuals with a high probability of undergoing coronary artery bypass grafting (prasugrel should not be started, or when possible, discontinue prasugrel at least 7 days before any surgery) (<a class="bibr" href="#clopidogrel.REF.29" rid="clopidogrel.REF.29">29</a>).</p><p>In an analysis from the PLATelet inhibition and patient Outcomes (PLATO) trial, ticagrelor was found to be superior to clopidogrel in a subgroup of individuals with ACS who were treated with PCI. Consistent with the overall results of the trial, ticagrelor was found to have superior efficacy and similar safety compared with clopidogrel (<a class="bibr" href="#clopidogrel.REF.30" rid="clopidogrel.REF.30">30</a>, <a class="bibr" href="#clopidogrel.REF.31" rid="clopidogrel.REF.31">31</a>, <a class="bibr" href="#clopidogrel.REF.32" rid="clopidogrel.REF.32">32</a>). Other studies have similarly observed a better response to ticagrelor for antiplatelet activities but noted an increased risk of bleeding when compared with clopidogrel for various indications (stroke, unstable angina, chronic coronary syndromes after PCI and other coronary artery diseases), which may be of particular concern in elderly individuals (<a class="bibr" href="#clopidogrel.REF.33" rid="clopidogrel.REF.33">33</a>, <a class="bibr" href="#clopidogrel.REF.34" rid="clopidogrel.REF.34">34</a>, <a class="bibr" href="#clopidogrel.REF.35" rid="clopidogrel.REF.35">35</a>, <a class="bibr" href="#clopidogrel.REF.36" rid="clopidogrel.REF.36">36</a>).</p><p>In addition, the latest guideline from the American College of Cardiology/American Heart Association includes a preference for alternative therapy (prasugrel or ticagrelor) over clopidogrel in individuals with ACS/PCI. This is a class IIa recommendation based on moderate quality, from the 2016 focused update on dual antiplatelet therapy (<a class="bibr" href="#clopidogrel.REF.37" rid="clopidogrel.REF.37">37</a>). In full, this recommendation states in individuals with ACS who are “treated with dual antiplatelet therapy after coronary stent implantation who are not at high risk for bleeding complications and who do not have a history of stroke or TIA, it is reasonable to choose prasugrel over clopidogrel for maintenance P2Y12 inhibitor therapy.” These recommendations also state that “it is reasonable to use ticagrelor in preference to clopidogrel for maintenance of P2Y12 inhibitor therapy.” (<a class="bibr" href="#clopidogrel.REF.37" rid="clopidogrel.REF.37">37</a>)</p><p>Although prasugrel and ticagrelor are often reported to be more effective than standard-dose clopidogrel, dual antiplatelet therapy with clopidogrel and aspirin remains the standard of care at many institutions for individuals with ACS undergoing PCI (<a class="bibr" href="#clopidogrel.REF.31" rid="clopidogrel.REF.31">31</a>, <a class="bibr" href="#clopidogrel.REF.38" rid="clopidogrel.REF.38">38</a>, <a class="bibr" href="#clopidogrel.REF.39" rid="clopidogrel.REF.39">39</a>, <a class="bibr" href="#clopidogrel.REF.40" rid="clopidogrel.REF.40">40</a>, <a class="bibr" href="#clopidogrel.REF.41" rid="clopidogrel.REF.41">41</a>). This may be because clopidogrel has a lower bleeding risk and is less expensive (<a class="bibr" href="#clopidogrel.REF.42" rid="clopidogrel.REF.42">42</a>). However, the availability of <i>CYP2C19</i> genetic testing can facilitate personalized antiplatelet therapy by pursuing alternative antiplatelet agents specifically for individuals with impaired CYP2C19 activity (<a class="bibr" href="#clopidogrel.REF.39" rid="clopidogrel.REF.39">39</a>, <a class="bibr" href="#clopidogrel.REF.43" rid="clopidogrel.REF.43">43</a>, <a class="bibr" href="#clopidogrel.REF.44" rid="clopidogrel.REF.44">44</a>, <a class="bibr" href="#clopidogrel.REF.45" rid="clopidogrel.REF.45">45</a>, <a class="bibr" href="#clopidogrel.REF.46" rid="clopidogrel.REF.46">46</a>).</p></div><div id="clopidogrel.Gene_CYP2C19"><h2 id="_clopidogrel_Gene_CYP2C19_">Gene: CYP2C19</h2><p>The cytochrome P450 superfamily (CYP) is a large and diverse group of enzymes that form the major system for metabolizing lipids, hormones, toxins, and drugs. The CYP genes are very polymorphic and can result in reduced, absent, or increased drug metabolism.</p><p>The CYP2C19 enzyme contributes to the metabolism of a range of clinically important drugs, such as antidepressants, benzodiazepines, voriconazole (<a class="bibr" href="#clopidogrel.REF.47" rid="clopidogrel.REF.47">47</a>), some proton pump inhibitors, and the antiplatelet agent, clopidogrel. The variability of clopidogrel metabolism and treatment outcomes between individuals is partly determined by variant alleles of the <i>CYP2C19</i> gene. The <i>CYP2C19</i> gene is highly polymorphic with over 35 variant star (*) alleles catalogued by the Pharmacogene Variation (<a href="https://www.pharmvar.org/gene/CYP2C19" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PharmVar</a>) Consortium. The <i>CYP2C19*1</i> is considered the wild type allele when no variants are detected and is categorized as normal enzyme activity and the “normal metabolizer” phenotype. It should be noted that the <i>CYP2C19*1</i> haplotype has been determined to have a single nucleotide polymorphism in the coding region; however, the frequency of the variant nucleotide (G) is nearly 94% globally and this missense variant does not alter protein function (<a class="bibr" href="#clopidogrel.REF.48" rid="clopidogrel.REF.48">48</a>, <a class="bibr" href="#clopidogrel.REF.49" rid="clopidogrel.REF.49">49</a>, <a class="bibr" href="#clopidogrel.REF.50" rid="clopidogrel.REF.50">50</a>).</p><p>The <i>CYP2C19*17</i> allele is associated with increased enzyme activity and, depending on the number of alleles present, is associated with the “rapid” (one <i>*17</i> allele) and “ultrarapid” (2 <i>*17</i> alleles) metabolizer phenotypes. Non-functional alleles include <i>CYP2C19*2</i> and <i>*3</i>. The <i>CYP2C19</i> IMs have one copy of an allele that encodes a non-functional enzyme (for example, <i>*1/*2</i>), whereas “PMs” have 2 non-functional alleles (for example, <i>*2/*2</i>, <i>*2/*3</i>) (<a href="/books/NBK84114/table/clopidogrel.T.activity_status_of_selecte/?report=objectonly" target="object" rid-ob="figobclopidogrelTactivitystatusofselecte">Table 5</a>).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figclopidogrelTactivitystatusofselecte"><a href="/books/NBK84114/table/clopidogrel.T.activity_status_of_selecte/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobclopidogrelTactivitystatusofselecte"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="clopidogrel.T.activity_status_of_selecte"><a href="/books/NBK84114/table/clopidogrel.T.activity_status_of_selecte/?report=objectonly" target="object" rid-ob="figobclopidogrelTactivitystatusofselecte">Table 5. </a></h4><p class="float-caption no_bottom_margin">Activity Status of Selected <i>CYP2C19</i> Alleles </p></div></div><p>Approximately 2% of Caucasians, 4% of African Americans, 14% of Chinese, and 57% of Oceanians are CYP2C19 PM; and up to 45% of individuals are CYP2C19 IM (<a class="bibr" href="#clopidogrel.REF.1" rid="clopidogrel.REF.1">1</a>, <a class="bibr" href="#clopidogrel.REF.2" rid="clopidogrel.REF.2">2</a>).</p><p>The most common no function variant is <i>CYP2C19*2</i>, which contains the <a href="/nuccore/4503218" class="bk_tag" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=nuccore">NM_000769.1</a>:c.681G>A variant in exon 5 that results in an aberrant splice site and produces a truncated and non-functioning protein. The <i>CYP2C19*2</i> allele frequencies are between 12–18% in individuals of European, American, or African ancestry, between 25–35% in Asians, Native Hawaiians, and Pacific Islanders, and up to 60% in Oceanian populations (<a class="bibr" href="#clopidogrel.REF.2" rid="clopidogrel.REF.2">2</a>, <a class="bibr" href="#clopidogrel.REF.52" rid="clopidogrel.REF.52">52</a>). Approximately 6–12% of the observed variability in antiplatelet effect of clopidogrel is thought to be attributed to <i>CYP2C19</i> variants (<a class="bibr" href="#clopidogrel.REF.53" rid="clopidogrel.REF.53">53</a>).</p><p>For <i>CYP2C19</i>, another commonly tested no functional variant is <i>CYP2C19*3</i>, which contains a c.636G>A variant in exon 4 that causes a premature stop codon. The <i>CYP2C19*3</i> allele frequencies are ~2–9% in Asian populations, but rare in other ancestral populations (<a class="bibr" href="#clopidogrel.REF.52" rid="clopidogrel.REF.52">52</a>). Other non-functional variants occur in less than 1% of the general population and include <i>CYP2C19*4</i>–<i>*8</i> (<a class="bibr" href="#clopidogrel.REF.54" rid="clopidogrel.REF.54">54</a>).</p><p>The frequency of the <i>CYP2C19*17</i> allele is approximately 22% in individuals of European ancestry, 8% for individuals from the Americas, 0.5–5.7% in Asian, Native Hawaiian, and Pacific Islander populations, 17% in African populations, and 20% in African American and Afro-Caribbean populations (<a class="bibr" href="#clopidogrel.REF.2" rid="clopidogrel.REF.2">2</a>, <a class="bibr" href="#clopidogrel.REF.52" rid="clopidogrel.REF.52">52</a>).</p><p>The <i>CYP2C19*2, *3,</i> and <i>*17</i> alleles are the ‘Tier 1’ alleles recommended by the Association for Molecular Pathology (AMP) to be included in <i>CYP2C19</i> clinical genotyping assays (<a class="bibr" href="#clopidogrel.REF.55" rid="clopidogrel.REF.55">55</a>). The AMP further recommends testing laboratories consider <i>*4A, *4B, *5, *6, *7, *8, *9, *10,</i> and <i>*35</i> alleles as optional ‘Tier 2’ alleles that have all been shown to have decreased or no function but have either a low minor allele frequency, limited data characterizing the impact on enzyme function, or lack reference materials. Among the ‘Tier 2’ alleles, the <i>CYP2C19*35</i> allele is most common, and has a frequency of 9% in African populations (<a class="bibr" href="#clopidogrel.REF.55" rid="clopidogrel.REF.55">55</a>).</p><p>
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<b>Phenoconversion due to CYP2C19 Inhibitors and Inducers</b>
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</p><p>Many medicines are metabolized by the CYP2C19 enzyme, and the activity level of the enzyme can be altered by administration of medications or supplements. Significant alterations in the effective enzyme activity level due to co-medication or other non-genetic factors is called phenoconversion. Increased enzymatic activity can be caused by induction of CYP2C19, such an effect can occur with medications like rifampin; this can lead to an increased bleeding risk due to increased activation of clopidogrel (<a class="bibr" href="#clopidogrel.REF.1" rid="clopidogrel.REF.1">1</a>). St. John’s wort and smoking may also increase CYP enzyme activity and increase the platelet inhibitory effect of clopidogrel (<a class="bibr" href="#clopidogrel.REF.56" rid="clopidogrel.REF.56">56</a>). Inhibitors of CYP2C19 activity can cause reduced clopidogrel metabolism and thus trigger a blunted response to the medication. The FDA-approved drug label cautions that co-medication with proton pump inhibitors (PPIs) omeprazole or esomeprazole can decrease the antiplatelet effects of clopidogrel (<a class="bibr" href="#clopidogrel.REF.1" rid="clopidogrel.REF.1">1</a>). One study found that co-medication with other CYP2C19 substrate medications was a significant risk factor for adverse drug reactions during clopidogrel treatment (<a class="bibr" href="#clopidogrel.REF.57" rid="clopidogrel.REF.57">57</a>).</p></div><div id="clopidogrel.Linking_CYP2C19_Genetic_Vari"><h2 id="_clopidogrel_Linking_CYP2C19_Genetic_Vari_">Linking <i>CYP2C19</i> Genetic Variation with Treatment Response</h2><p>Several studies have reported an increase in adverse cardiovascular events in individuals who have one or 2 no function <i>CYP2C19</i> alleles (namely, IM or PM), compared with individuals with 2 normal copies of the <i>CYP2C19</i> gene (normal metabolizer). These studies focused on individuals with ACS undergoing PCI, with individuals who had no function alleles also being at a higher risk of stent thrombosis or major adverse cardiovascular and cerebrovascular events (<a class="bibr" href="#clopidogrel.REF.58" rid="clopidogrel.REF.58">58</a>, <a class="bibr" href="#clopidogrel.REF.59" rid="clopidogrel.REF.59">59</a>, <a class="bibr" href="#clopidogrel.REF.60" rid="clopidogrel.REF.60">60</a>, <a class="bibr" href="#clopidogrel.REF.61" rid="clopidogrel.REF.61">61</a>, <a class="bibr" href="#clopidogrel.REF.62" rid="clopidogrel.REF.62">62</a>). These individuals may require much higher doses of clopidogrel (2- to 4-fold higher) or an alternative drug (<a class="bibr" href="#clopidogrel.REF.63" rid="clopidogrel.REF.63">63</a>, <a class="bibr" href="#clopidogrel.REF.64" rid="clopidogrel.REF.64">64</a>, <a class="bibr" href="#clopidogrel.REF.65" rid="clopidogrel.REF.65">65</a>). A meta-analysis of 7 randomized control trials and 4 non-randomized control trials found a significant association between <i>CYP2C19</i> loss-of-function allele carriers and poorer outcomes when treated with clopidogrel as compared with an alternative P2Y<sub>12</sub> inhibitor (<a class="bibr" href="#clopidogrel.REF.9" rid="clopidogrel.REF.9">9</a>). This analysis was limited to studies of individuals with ACS with at least 50% of participants undergoing PCI, where <i>CYP2C19</i> genotype was assessed and included in the outcomes, and clopidogrel was compared with an alternative medication. Some clinical studies did not find a significant association between <i>CYP2C19</i> and clinical outcome in individuals with ACS; however, these often included data from lower risk non-PCI individuals (<a class="bibr" href="#clopidogrel.REF.66" rid="clopidogrel.REF.66">66</a>, <a class="bibr" href="#clopidogrel.REF.67" rid="clopidogrel.REF.67">67</a>, <a class="bibr" href="#clopidogrel.REF.68" rid="clopidogrel.REF.68">68</a>).</p><p>Several studies of individuals with TIA have reported that CYP2C19 status influences the risk of having an ischemic stroke or adverse clinical outcomes following a stroke when treated with clopidogrel (<a class="bibr" href="#clopidogrel.REF.69" rid="clopidogrel.REF.69">69</a>, <a class="bibr" href="#clopidogrel.REF.70" rid="clopidogrel.REF.70">70</a>, <a class="bibr" href="#clopidogrel.REF.71" rid="clopidogrel.REF.71">71</a>, <a class="bibr" href="#clopidogrel.REF.72" rid="clopidogrel.REF.72">72</a>). One trial (CHANCE – Clopidogrel in High-risk Individuals with Acute Nondisabling Cerebrovascular Events; study size of 5,170 individuals) found that the use of clopidogrel plus aspirin compared with aspirin alone reduced the risk of a new stroke only in the subgroup of individuals who did not have the <i>CYP2C19</i> no function alleles (<a class="bibr" href="#clopidogrel.REF.73" rid="clopidogrel.REF.73">73</a>). The CHANCE-2 trial (study size 6,412 individuals) examined the superiority of ticagrelor to clopidogrel for <i>CYP2C19</i> loss-of-function allele carriers following TIA or minor ischemic stroke and found a modest but significant improvement in the rate of strokes in the first 90 days with no significant differences in risk of severe or moderate bleeding with either P2Y<sub>12</sub> inhibitor (<a class="bibr" href="#clopidogrel.REF.74" rid="clopidogrel.REF.74">74</a>). Additional trials examining various antiplatelet regimens following stroke or TIA have been recently reviewed, which supports the role of <i>CYP2C19</i> genotype in contributing to potential risks with clopidogrel therapy for stroke or TIA (<a class="bibr" href="#clopidogrel.REF.72" rid="clopidogrel.REF.72">72</a>). At least one study of <i>CYP2C19</i> variation and clopidogrel effectiveness in neurovascular conditions found an opposite effect of <i>CYP2C19</i> loss-of-function variants on poor treatment response. The authors of this study concluded more research was needed to fully understand the impact of these variants in the context of intracranial atherosclerotic disease; however, caution should be taken when considering these findings as the study only included 188 individuals (<a class="bibr" href="#clopidogrel.REF.75" rid="clopidogrel.REF.75">75</a>).</p><p>Recent studies have found that <i>CYP2C19</i>-genotype-guided antiplatelet therapy results in a higher likelihood of achieving a therapeutic level of on-treatment platelet reactivity (<a class="bibr" href="#clopidogrel.REF.11" rid="clopidogrel.REF.11">11</a>, <a class="bibr" href="#clopidogrel.REF.76" rid="clopidogrel.REF.76">76</a>, <a class="bibr" href="#clopidogrel.REF.77" rid="clopidogrel.REF.77">77</a>, <a class="bibr" href="#clopidogrel.REF.78" rid="clopidogrel.REF.78">78</a>). Genotype-guided therapy may also be cost effective among ACS individuals undergoing PCI (<a class="bibr" href="#clopidogrel.REF.39" rid="clopidogrel.REF.39">39</a>, <a class="bibr" href="#clopidogrel.REF.79" rid="clopidogrel.REF.79">79</a>, <a class="bibr" href="#clopidogrel.REF.80" rid="clopidogrel.REF.80">80</a>, <a class="bibr" href="#clopidogrel.REF.81" rid="clopidogrel.REF.81">81</a>). However, many authors, including the American Heart Association, find more data are needed to determine whether routine genotyping and platelet function tests could help reduce future cardiovascular events in ACS individuals or for secondary stroke prevention (<a class="bibr" href="#clopidogrel.REF.37" rid="clopidogrel.REF.37">37</a>, <a class="bibr" href="#clopidogrel.REF.82" rid="clopidogrel.REF.82">82</a>, <a class="bibr" href="#clopidogrel.REF.83" rid="clopidogrel.REF.83">83</a>, <a class="bibr" href="#clopidogrel.REF.84" rid="clopidogrel.REF.84">84</a>, <a class="bibr" href="#clopidogrel.REF.85" rid="clopidogrel.REF.85">85</a>).</p></div><div id="clopidogrel.Genetic_Testing"><h2 id="_clopidogrel_Genetic_Testing_">Genetic Testing</h2><p>Clinical genotyping tests are available for several <i>CYP2C19</i> alleles. The NIH’s Genetic Testing Registry (GTR) provides examples of genetic tests that are available for <a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=C2674941" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">clopidogrel response</a><u>, </u><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=C1836023" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CYP2C19-related poor drug metabolism</a>, and the <a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=1557%5Bgeneid%5D" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri"><i>CYP2C19</i> gene</a>.</p><p>Usually, an individual’s result is reported as a diplotype, such as <i>CYP2C19 *1/*1</i>, and may also include an interpretation of the individual’s predicted metabolizer phenotype (ultrarapid, rapid, normal, intermediate, or poor). When a test report does not provide a predicted metabolizer phenotype, resources such as <a href="https://www.pharmgkb.org/page/pharmvar" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PharmVar</a> and <a href="https://pharmcat.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PharmCAT</a> are available to assist with predicting the functional impact of identified variants.</p><p>The association between <i>CYP2C19*2</i> and <i>*3</i> and clopidogrel response has been extensively studied; however, the less common no function alleles (for example, <i>CYP2C19*4</i>–<i>*8</i>) also likely influence clopidogrel response similar to <i>*2</i> and <i>*3,</i> but the body of evidence is not as extensive. Therefore, these alleles should be considered to reduce the effectiveness of clopidogrel therapy in a similar manner to the more common <i>CYP2C19*2</i> allele (<a class="bibr" href="#clopidogrel.REF.54" rid="clopidogrel.REF.54">54</a>, <a class="bibr" href="#clopidogrel.REF.86" rid="clopidogrel.REF.86">86</a>). Guidance regarding inclusion of specific alleles for clinical testing is available from AMP (<a class="bibr" href="#clopidogrel.REF.55" rid="clopidogrel.REF.55">55</a>). The current recommendations from CPIC advise management of likely PMs and likely IMs as if these individuals were definitively in the predicted phenotype group (<a class="bibr" href="#clopidogrel.REF.3" rid="clopidogrel.REF.3">3</a>).</p></div><div id="clopidogrel.The_CYP2C19_Gene_Interaction"><h2 id="_clopidogrel_The_CYP2C19_Gene_Interaction_">The <i>CYP2C19</i> Gene Interactions with Medications Used for Additional Indications</h2><p>The CYP2C19 enzyme metabolizes many medications and may have impacts on other conditions. Other medications affected by <i>CYP2C19</i> genetic variation may be used to treat:</p><ul><li class="half_rhythm"><div>Gastrointestinal ulcers, gastroesophageal reflux, erosive esophagitis, and <i>Helicobacter pylori</i> infection—PPIs like <a href="/books/n/gtrbook/omeprazole/?report=reader">omeprazole</a>, <a href="/books/n/gtrbook/esomeprazole/?report=reader">esomeprazole</a>, and others may have reduced metabolism in CYP2C19 IMs and PMs and thus these individuals have higher exposure to these medications, which imparts risk of adverse events. Conversely, <i>CYP2C19*17</i> confers increased activity and thus a more rapid clearance of PPIs and potential for treatment failure in ultrarapid metabolizers (UMs).</div></li><li class="half_rhythm"><div>Antifungal treatment—<a href="/books/n/gtrbook/voriconazole/?report=reader">voriconazole</a> is metabolized by CYP2C19 and UMs may have delayed target blood concentrations due to rapid clearance; PMs may experience high exposure and have a risk of adverse events.</div></li><li class="half_rhythm"><div>Depression, anxiety disorders, obsessive-compulsive disorder, or migraine prophylaxis—both selective serotonin reuptake inhibitors (SSRIs, such as citalopram, escitalopram, and sertraline) and tricyclic antidepressants (TCAs, such as the tertiary amines <a href="/books/n/gtrbook/amitriptyline/?report=reader">amitriptyline</a>, clomipramine, doxepin, <a href="/books/n/gtrbook/imipramine/?report=reader">imipramine</a>, and trimipramine) can be metabolized by CYP2C19. When administering SSRIs, UMs may experience treatment failure due to high clearance while PMs may require dose reduction. For the tertiary amine TCAs, UMs may experience altered responses or side effects due to rapid conversion to secondary amines while PMs are at risk of suboptimal responses and may require a lower dose. <a href="/books/n/gtrbook/diazepam/?report=reader">Diazepam</a> is also partially metabolized by CYP2C19 and altered enzyme function may contribute to altered clearance of this medication.</div></li><li class="half_rhythm"><div>Epilepsy or seizures—<a href="/books/n/gtrbook/brivaracetam/?report=reader">brivaracetam</a>, used for partial-onset (focal) epilepsy, is partially metabolized by CYP2C19 and PMs may require lower doses to avoid adverse effects due to reduced clearance of this medication. <a href="/books/n/gtrbook/clobazam/?report=reader">Clobazam</a> is used to manage seizures in a variety of conditions and CYP2C19 PMs may experience higher exposure to norclobazam, putting them at higher risk for adverse effects. <a href="/books/n/gtrbook/lacosamide/?report=reader">Lacosamide</a> is also metabolized by CYP2C19, though there is no indication that PMs require altered dosing or management.</div></li><li class="half_rhythm"><div>Musculoskeletal pain—<a href="/books/n/gtrbook/carisoprodol/?report=reader">carisoprodol</a>, a centrally acting muscle relaxant, is metabolized by CYP2C19 and PMs may be at a higher risk of carisoprodol toxicity.</div></li><li class="half_rhythm"><div>Hypoactive sexual desire disorder—<a href="/books/n/gtrbook/flibanserin/?report=reader">flibanserin</a> is metabolized, in part, by CYP2C19 and PMs have a higher exposure to this medication, resulting in an elevated risk of hypotension, syncope, and CNS depression.</div></li></ul><p>Additional information on gene-drug interactions for <i>CYP2C19</i> are available from <a href="https://www.pharmgkb.org/gene/PA124/overview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PharmGKB</a>, <a href="https://cpicpgx.org/genes-drugs/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CPIC</a> and the <a href="https://www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">FDA</a> (search for “CYP2C19”).</p></div><div id="clopidogrel.Therapeutic_Recommendations"><h2 id="_clopidogrel_Therapeutic_Recommendations_">Therapeutic Recommendations based on Genotype</h2><p><b>This section contains excerpted</b><sup><a href="#clopidogrel.FN1">1</a></sup>
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<b>information on gene-based dosing recommendations. Neither this section nor other parts of this review contain the complete recommendations from the sources.</b></p><div id="clopidogrel.2022_Statement_from_the_US_F"><h3>2022 Statement from the US Food and Drug Administration (FDA)</h3><p>WARNING: DIMINISHED ANTIPLATELET EFFECT IN PATIENTS WITH TWO LOSS-OF-FUNCTION ALLELES OF THE CYP2C19 GENE</p><p>The effectiveness of clopidogrel bisulfate results from its antiplatelet activity, which is dependent on its conversion to an active metabolite by the cytochrome P450 (CYP) system, principally CYP2C19 … Clopidogrel bisulfate at recommended doses forms less of the active metabolite and so has a reduced effect on platelet activity in patients who are homozygous for nonfunctional alleles of the CYP2C19 gene, (termed "CYP2C19 poor metabolizers"). Tests are available to identify patients who are CYP2C19 poor metabolizers … Consider use of another platelet P2Y12 inhibitor in patients identified as CYP2C19 poor metabolizers.</p><p>[…]</p><p>Clopidogrel is a prodrug. Inhibition of platelet aggregation by clopidogrel is achieved through an active metabolite. The metabolism of clopidogrel to its active metabolite can be impaired by genetic variations in CYP2C19 … The metabolism of clopidogrel can also be impaired by drugs that inhibit CYP2C19, such as omeprazole or esomeprazole. Avoid concomitant use of clopidogrel bisulfate with omeprazole or esomeprazole because both significantly reduce the antiplatelet activity of clopidogrel bisulfate.</p><p>[…]</p><p>Rifampin strongly induces CYP2C19 resulting to both an increase level of clopidogrel active metabolite and platelet inhibition, which in particular might potentiate the risk of bleeding. As a precaution, avoid concomitant use of strong CYP2C19 inducers. […]</p><p>Clopidogrel is metabolized to its active metabolite in part by CYP2C19. Concomitant use of drugs that inhibit the activity of this enzyme results in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition… Avoid concomitant use of clopidogrel bisulfate with omeprazole or esomeprazole.</p><p>[…]</p><p>CYP2C19 is involved in the formation of both the active metabolite and the 2-oxoclopidogrel intermediate metabolite. Clopidogrel active metabolite pharmacokinetics and antiplatelet effects, as measured by ex vivo platelet aggregation assays, differ according to CYP2C19 genotype. Patients who are homozygous for nonfunctional alleles of the CYP2C19 gene are termed "CYP2C19 poor metabolizers." Approximately 2% of White and 4% of Black patients are poor metabolizers; the prevalence of poor metabolism is higher in Asian patients (e.g., 14% of Chinese). Tests are available to identify patients who are CYP2C19 poor metabolizers.</p><p><b>Please review the complete therapeutic recommendations that are located here: (</b><a class="bibr" href="#clopidogrel.REF.1" rid="clopidogrel.REF.1"><b>1</b></a><b>)</b>.</p></div><div id="clopidogrel.2022_Statement_from_the_Clin"><h3>2022 Statement from the Clinical Pharmacogenetics Implementation Consortium (CPIC)</h3><p>In patients with ACS and/or undergoing PCI…avoid clopidogrel in CYP2C19 Ims and PMs and use an alternative antiplatelet agent, such as prasugrel or ticagrelor, if no contraindications.</p><p>[…]</p><p>If considering clopidogrel and the patient is a CYP2C19 NM, the standard dose (75 mg/day) is recommended. Although clopidogrel-treated CYP2C19 RMs and Ums may experience lower on-treatment platelet reactivity compared with NMs, clinical data also support the use of clopidogrel at standard doses in CYP2C19 RMs and Ums due to the lack of evidence demonstrating significant differences in risk of bleeding or ischemic events compared with NMs in patients undergoing PCI.</p><p>[…]</p><p>There remain limited data regarding the potential benefit of CYP2C19-guided antiplatelet therapy on outcomes exclusively in patients undergoing PCI for a non-ACS indication. Patients undergoing elective PCI have a lower risk of cardiovascular events compared with patients with ACS, but were included in multiple studies evaluating outcomes of genotype-guided antiplatelet therapy, including the IGNITE and TAILOR-PCI studies (Table S2). Therefore, the therapeutic recommendations for patients with ACS and/or undergoing PCI may also be considered for patients undergoing elective PCI.</p><p>[…]</p><p>In patients with a cardiovascular indication for clopidogrel outside the setting of an ACS or PCI, including the treatment of patients with peripheral arterial disease or stable coronary artery disease following a recent MI, the standard dose (75 mg/day) is recommended if the patient is a CYP2C19 NM. However, there are insufficient data to make a clinical recommendation for CYP2C19 Ums, RMs, and Ims. If the patient is a CYP2C19 PM, it is recommended to avoid clopidogrel and use prasugrel or ticagrelor at standard doses if no contraindication.</p><p>[…]</p><p>If considering clopidogrel for patients with neurovascular disease, including the treatment of acute ischemic stroke or TIA, the secondary prevention of stroke, or the prevention of thromboembolic events following neurointerventional procedures, such as carotid artery stenting and endarterectomy and stent-assisted coiling of intracranial aneurysms, the standard dose (75 mg/day) is recommended in CYP2C19 NMs (<a href="/books/NBK84114/table/clopidogrel.T.the_cpic_2022_antiplatelet_1/?report=objectonly" target="object" rid-ob="figobclopidogrelTthecpic2022antiplatelet1">Table 3</a>). In CYP2C19 Ims and PMs, there is a “moderate” recommendation to avoid clopidogrel if possible and consider an alternative P2Y12 inhibitor at standard doses if clinically indicated and no contraindication. Alternative P2Y12 inhibitors not impacted by <i>CYP2C19</i> genetic variants with indications for patients with stroke include ticagrelor and ticlopidine. However, ticlopidine has serious hematological adverse effects that also need to be considered. Prasugrel is contraindicated in patients with a history of stroke or TIA.</p><p><b>Please review the complete therapeutic recommendations that are located here:</b> (<a class="bibr" href="#clopidogrel.REF.3" rid="clopidogrel.REF.3">3</a>)</p></div><div id="clopidogrel.2019_Summary_of_Recommendati"><h3>2019 Summary of Recommendations from the Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Association for the Advancement of Pharmacy (KNMP)</h3><p>CYP2C19 PM: CLOPIDOGREL</p><p>The risk of serious cardiovascular and cerebrovascular events is increased in patients undergoing balloon angioplasty or stent placement (percutaneous coronary intervention) and in patients with a stroke or TIA, because the genetic variation reduces the activation of clopidogrel. No negative clinical consequences have been proved in other patients.</p><ul><li class="half_rhythm"><div>PERCUTANEOUS CORONARY INTERVENTION, STROKE or TIA:</div><ul><li class="half_rhythm"><div>avoid clopidogrel</div></li><li class="half_rhythm"><div>Prasugrel, ticagrelor and acetylsalicylic acid/dipyridamole are not metabolised by CYP2C19 (or to a lesser extent).</div></li></ul></li><li class="half_rhythm"><div>OTHER INDICATIONS:</div><ul><li class="half_rhythm"><div>determine the level of inhibition of platelet aggregation by clopidogrel</div></li><li class="half_rhythm"><div>consider an alternative in poor responders</div></li><li class="half_rhythm"><div>Prasugrel and ticagrelor are not metabolised by CYP2C19 (or to a lesser extent).</div></li></ul></li></ul><p>CYP2C19 IM: clopidogrel</p><p>The risk of serious cardiovascular and cerebrovascular events is increased in patients undergoing balloon angioplasty or stent placement (percutaneous coronary intervention) and in patients with a stroke or TIA, as the genetic variation reduces the activation of clopidogrel. No negative clinical consequences have been observed in other patients.</p><ul><li class="half_rhythm"><div>PERCUTANEOUS CORONARY INTERVENTION, STROKE or TIA:</div><ul><li class="half_rhythm"><div>choose an alternative or double the dose to 150 mg/day (600 mg loading dose); Prasugrel, ticagrelor and acetylsalicylic acid/dipyridamole are not metabolised by CYP2C19 (or to a lesser extent).</div></li></ul></li><li class="half_rhythm"><div>OTHER INDICATIONS:</div><ul><li class="half_rhythm"><div>no action required</div></li></ul></li></ul><p>CYP2C19 UM: clopidogrel</p><p>NO action is required for this gene-drug interaction.</p><p>The genetic variation results in increased conversion of clopidogrel to the active metabolite. However, this can result in both positive effects (reduction in the risk of serious cardiovascular and cerebrovascular events) and negative effects (increase in the risk of bleeding).</p><p><b>Please review the complete therapeutic recommendations that are located here: (</b><a class="bibr" href="#clopidogrel.REF.4" rid="clopidogrel.REF.4"><b>4</b></a><b>)</b>.</p></div></div><div id="clopidogrel.Nomenclature_of_Selected_CYP"><h2 id="_clopidogrel_Nomenclature_of_Selected_CYP_">Nomenclature of Selected <i>CYP2C19</i> Alleles</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figclopidogrelTe"><a href="/books/NBK84114/table/clopidogrel.Te/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobclopidogrelTe"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="clopidogrel.Te"><a href="/books/NBK84114/table/clopidogrel.Te/?report=objectonly" target="object" rid-ob="figobclopidogrelTe">Table</a></h4></div></div></div><div id="clopidogrel.Acknowledgments"><h2 id="_clopidogrel_Acknowledgments_">Acknowledgments</h2><p>The authors would like to acknowledge Amber Beitelshees, PharmD, MPH, FAHA, FCCP, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA, and John McDermott, MRes, BSc, MBChB, NIHR Doctoral Research Fellow, University of Manchester, Clinical Genetics Registrar, Manchester University NHS Foundation Trust, Manchester, UK for reviewing this summary.</p><p>
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<b>Third edition:</b>
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</p><p>The author would like to thank Larisa H. Cavallari, PharmD, Associate Professor, Department of Pharmacotherapy and Translational Research & Director, Center for Pharmacogenomics, University of Florida, FLA, USA; Inge Holsappel, Pharmacist, Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Association for the Advancement of Pharmacy (KNMP), The Hague, The Netherlands; and Gerasimos Siasos, MD, PhD, FCCP, FACC, Associate Professor, Department of Cardiology, ‘Hippokration’ General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece, and Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical, Boston, MA, USA, for reviewing this summary.</p><p>
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<b>Second edition:</b>
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</p><p>The author would like to thank Stuart A. Scott, Assistant Professor of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; and Dietmar Trenk, Head of Clinical Pharmacology at the University Heart Center, Bad Krozingen and Professor at the Albert Ludwig University of Freiburg, Freiburg, Germany, for reviewing this summary.</p></div><div id="clopidogrel.Version_History"><h2 id="_clopidogrel_Version_History_">Version History</h2><p>To view the 2018 version of this summary (Created: April 18, 2018) please click <a href="/books/NBK84114/bin/20180418_clopidogrel.pdf">here</a>.</p><p>To view the 2015 version of this summary (Created: November 19, 2015) please click <a href="/books/NBK84114/bin/20151119clopidogrel.pdf">here.</a></p><p>To view the 2013 version of this summary (Created: March 18, 2013) please click <a href="/books/NBK84114/bin/20130318_clopidogrel.pdf">here</a>.</p><p>To view the 2012 version of this summary (Created: March 8, 2012) please click <a href="/books/NBK84114/bin/20120308_clopidogrel.pdf">here</a>.</p></div><div id="clopidogrel.References"><h2 id="_clopidogrel_References_">References</h2><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><div class="bk_ref" id="clopidogrel.REF.1">CLOPIDOGREL BISULFATE- clopidogrel bisulfate tablet. Torrent Pharmaceuticals Limited; 2022. Available from: <a href="https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ae07b785-b522-41c6-b27c-24c4d5cd814d" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://dailymed<wbr style="display:inline-block"></wbr>​.nlm<wbr style="display:inline-block"></wbr>​.nih.gov/dailymed/drugInfo<wbr style="display:inline-block"></wbr>​.cfm?setid=ae07b785-b522-41c6-b27c-24c4d5cd814d</a>.</div></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><div class="bk_ref" id="clopidogrel.REF.2">CYP2C19 frequency table [Cited 29 Sept 2022]. Available from: <a href="https://files.cpicpgx.org/data/report/current/frequency/CYP2C19_frequency_table.xlsx" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://files<wbr style="display:inline-block"></wbr>​.cpicpgx<wbr style="display:inline-block"></wbr>​.org/data/report/current<wbr style="display:inline-block"></wbr>​/frequency/CYP2C19_frequency_table<wbr style="display:inline-block"></wbr>​.xlsx</a>.</div></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><div class="bk_ref" id="clopidogrel.REF.3">Lee C.R., Luzum J.A., Sangkuhl K., Gammal R.S., et al. Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 Genotype and Clopidogrel Therapy: 2022 Update. <span><span class="ref-journal">Clin Pharmacol Ther. </span>2022</span> [<a href="/pmc/articles/PMC9287492/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9287492</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35034351" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35034351</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><div class="bk_ref" id="clopidogrel.REF.4">Royal Dutch Pharmacists Association (KNMP). Dutch Pharmacogenetics Working Group (DPWG). Pharmacogenetic Guidelines [Internet]. Netherlands. Clopidogrel – CYP2C19 [Cited 1 Feb 2022]. Available from: <a href="https://www.knmp.nl/dossiers/farmacogenetica" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://www<wbr style="display:inline-block"></wbr>​.knmp.nl/dossiers<wbr style="display:inline-block"></wbr>​/farmacogenetica</a>.</div></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><div class="bk_ref" id="clopidogrel.REF.5">CLOPIDOGREL BISULFATE- clopidogrel tablet, film coated [package insert]. Morgantown, WV Inc., M.P.; 2017. Available from: <a href="https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a9a3c560-2408-4dd0-9f83-ee3e3a549c7b" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://dailymed<wbr style="display:inline-block"></wbr>​.nlm<wbr style="display:inline-block"></wbr>​.nih.gov/dailymed/drugInfo<wbr style="display:inline-block"></wbr>​.cfm?setid=a9a3c560-2408-4dd0-9f83-ee3e3a549c7b</a>.</div></dd></dl><dl class="bkr_refwrap"><dt>6.</dt><dd><div class="bk_ref" id="clopidogrel.REF.6">A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. <span><span class="ref-journal">Lancet. </span>1996;<span class="ref-vol">348</span>(9038):1329–39.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8918275" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8918275</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>7.</dt><dd><div class="bk_ref" id="clopidogrel.REF.7">Yusuf S., Zhao F., Mehta S.R., Chrolavicius S., et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. <span><span class="ref-journal">N Engl J Med. </span>2001;<span class="ref-vol">345</span>(7):494–502.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11519503" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11519503</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>8.</dt><dd><div class="bk_ref" id="clopidogrel.REF.8">Chen Z.M., Jiang L.X., Chen Y.P., Xie J.X., et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. <span><span class="ref-journal">Lancet. </span>2005;<span class="ref-vol">366</span>(9497):1607–21.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16271642" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16271642</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>9.</dt><dd><div class="bk_ref" id="clopidogrel.REF.9">Castrichini M., Luzum J.A., Pereira N. Pharmacogenetics of Antiplatelet Therapy. <span><span class="ref-journal">Annu Rev Pharmacol Toxicol. </span>2022</span> [<a href="/pmc/articles/PMC9868113/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9868113</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35914768" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35914768</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>10.</dt><dd><div class="bk_ref" id="clopidogrel.REF.10">Mallouk N., Labruyere C., Reny J.L., Chapelle C., et al. Prevalence of poor biological response to clopidogrel: a systematic review. <span><span class="ref-journal">Thromb Haemost. </span>2012;<span class="ref-vol">107</span>(3):494–506.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22273694" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22273694</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>11.</dt><dd><div class="bk_ref" id="clopidogrel.REF.11">So D.Y., Wells G.A., McPherson R., Labinaz M., et al. A prospective randomized evaluation of a pharmacogenomic approach to antiplatelet therapy among patients with ST-elevation myocardial infarction: the RAPID STEMI study. <span><span class="ref-journal">Pharmacogenomics J. </span>2016;<span class="ref-vol">16</span>(1):71–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25850030" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25850030</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>12.</dt><dd><div class="bk_ref" id="clopidogrel.REF.12">Legrand D., Barbato E., Chenu P., Magne J., et al. The STIB score: a simple clinical test to predict clopidogrel resistance. <span><span class="ref-journal">Acta Cardiol. </span>2015;<span class="ref-vol">70</span>(5):516–21.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26567810" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26567810</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>13.</dt><dd><div class="bk_ref" id="clopidogrel.REF.13">Lin L., Wang H., Chen Y.F., Lin W.W., et al. High maintenance dose of clopidogrel in patients with high on-treatment platelet reactivity after a percutaneous coronary intervention: a meta-analysis. <span><span class="ref-journal">Coron Artery Dis. </span>2015;<span class="ref-vol">26</span>(5):386–95.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25886999" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25886999</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>14.</dt><dd><div class="bk_ref" id="clopidogrel.REF.14">Zhou K., Yu S., Li J., Tan Y., et al. High on-treatment platelet reactivity is associated with poor outcomes after ischemic stroke: A meta-analysis. <span><span class="ref-journal">Acta Neurol Scand. </span>2022;<span class="ref-vol">146</span>(3):205–224.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/35652290" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35652290</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>15.</dt><dd><div class="bk_ref" id="clopidogrel.REF.15">Calderón-Cruz B., Rodriguez-Galvan K., Manzo-Francisco L.A., Vargas-Alarcon G., et al. C3435T polymorphism of the ABCB1 gene is associated with poor clopidogrel responsiveness in a Mexican population undergoing percutaneous coronary intervention. <span><span class="ref-journal">Thromb Res. </span>2015;<span class="ref-vol">136</span>(5):894–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26362473" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26362473</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>16.</dt><dd><div class="bk_ref" id="clopidogrel.REF.16">Díaz-Villamarín X., Davila-Fajardo C.L., Martinez-Gonzalez L.J., Carmona-Saez P., et al. Genetic polymorphisms influence on the response to clopidogrel in peripheral artery disease patients following percutaneous transluminal angioplasty. <span><span class="ref-journal">Pharmacogenomics. </span>2016;<span class="ref-vol">17</span>(12):1327–38.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27464309" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27464309</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>17.</dt><dd><div class="bk_ref" id="clopidogrel.REF.17">Zhai Y., He H., Ma X., Xie J., et al. Meta-analysis of effects of ABCB1 polymorphisms on clopidogrel response among patients with coronary artery disease. <span><span class="ref-journal">Eur J Clin Pharmacol. </span>2017;<span class="ref-vol">73</span>(7):843–854.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28378058" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28378058</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>18.</dt><dd><div class="bk_ref" id="clopidogrel.REF.18">Bouman H.J., Schomig E., van Werkum J.W., Velder J., et al. Paraoxonase-1 is a major determinant of clopidogrel efficacy. <span><span class="ref-journal">Nat Med. </span>2011;<span class="ref-vol">17</span>(1):110–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21170047" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21170047</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>19.</dt><dd><div class="bk_ref" id="clopidogrel.REF.19">Scott S.A., Collet J.P., Baber U., Yang Y., et al. Exome sequencing of extreme clopidogrel response phenotypes identifies B4GALT2 as a determinant of on-treatment platelet reactivity. <span><span class="ref-journal">Clin Pharmacol Ther. </span>2016;<span class="ref-vol">100</span>(3):287–94.</span> [<a href="/pmc/articles/PMC4982803/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4982803</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27213804" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27213804</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>20.</dt><dd><div class="bk_ref" id="clopidogrel.REF.20">Li M., Wang H., Xuan L., Shi X., et al. Associations between P2RY12 gene polymorphisms and risks of clopidogrel resistance and adverse cardiovascular events after PCI in patients with acute coronary syndrome. <span><span class="ref-journal">Medicine (Baltimore). </span>2017;<span class="ref-vol">96</span>(14):e6553. </span> p. [<a href="/pmc/articles/PMC5411211/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5411211</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28383427" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28383427</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>21.</dt><dd><div class="bk_ref" id="clopidogrel.REF.21">Yi X., Wang Y., Lin J., Cheng W., et al. Interaction of CYP2C19, P2Y12, and GPIIIa Variants Associates With Efficacy of Clopidogrel and Adverse Events on Patients With Ischemic Stroke. <span><span class="ref-journal">Clin Appl Thromb Hemost. </span>2017;<span class="ref-vol">23</span>(7):761–768.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27233747" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27233747</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>22.</dt><dd><div class="bk_ref" id="clopidogrel.REF.22">Yi X., Zhou Q., Wang C., Lin J., et al. Platelet receptor Gene (P2Y12, P2Y1) and platelet glycoprotein Gene (GPIIIa) polymorphisms are associated with antiplatelet drug responsiveness and clinical outcomes after acute minor ischemic stroke. <span><span class="ref-journal">Eur J Clin Pharmacol. </span>2017;<span class="ref-vol">73</span>(4):437–443.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28091702" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28091702</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>23.</dt><dd><div class="bk_ref" id="clopidogrel.REF.23">Lewis J.P., Horenstein R.B., Ryan K., O'Connell J.R., et al. The functional G143E variant of carboxylesterase 1 is associated with increased clopidogrel active metabolite levels and greater clopidogrel response. <span><span class="ref-journal">Pharmacogenet Genomics. </span>2013;<span class="ref-vol">23</span>(1):1–8.</span> [<a href="/pmc/articles/PMC3682407/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3682407</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23111421" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23111421</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>24.</dt><dd><div class="bk_ref" id="clopidogrel.REF.24">Franchini M., Mannucci P.M. New antiplatelet agents: why they are needed. <span><span class="ref-journal">Eur J Intern Med. </span>2009;<span class="ref-vol">20</span>(8):733–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19892299" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19892299</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>25.</dt><dd><div class="bk_ref" id="clopidogrel.REF.25">Wiviott S.D., Braunwald E., McCabe C.H., Montalescot G., et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. <span><span class="ref-journal">N Engl J Med. </span>2007;<span class="ref-vol">357</span>(20):2001–15.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17982182" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17982182</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>26.</dt><dd><div class="bk_ref" id="clopidogrel.REF.26">Wiviott S.D., Braunwald E., McCabe C.H., Horvath I., et al. Intensive oral antiplatelet therapy for reduction of ischaemic events including stent thrombosis in patients with acute coronary syndromes treated with percutaneous coronary intervention and stenting in the TRITON-TIMI 38 trial: a subanalysis of a randomised trial. <span><span class="ref-journal">Lancet. </span>2008;<span class="ref-vol">371</span>(9621):1353–63.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18377975" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18377975</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>27.</dt><dd><div class="bk_ref" id="clopidogrel.REF.27">Antman E.M., Wiviott S.D., Murphy S.A., Voitk J., et al. Early and late benefits of prasugrel in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction) analysis. <span><span class="ref-journal">J Am Coll Cardiol. </span>2008;<span class="ref-vol">51</span>(21):2028–33.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18498956" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18498956</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>28.</dt><dd><div class="bk_ref" id="clopidogrel.REF.28">Mariani M., Mariani G., De Servi S. Efficacy and safety of prasugrel compared with clopidogrel in patients with acute coronary syndromes: results of TRITON-TIMI 38 trials. <span><span class="ref-journal">Expert Rev Cardiovasc Ther. </span>2009;<span class="ref-vol">7</span>(1):17–23.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19105763" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19105763</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>29.</dt><dd><div class="bk_ref" id="clopidogrel.REF.29">PRASUGREL tablet, film coated [Package insert]. Morgantown, WV, USA: Mylan Pharmaceuticals Inc.; 2022. Available from: <a href="https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=41a4e332-6725-4cb7-940a-8291cf56cfe4" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://dailymed<wbr style="display:inline-block"></wbr>​.nlm<wbr style="display:inline-block"></wbr>​.nih.gov/dailymed/drugInfo<wbr style="display:inline-block"></wbr>​.cfm?setid=41a4e332-6725-4cb7-940a-8291cf56cfe4</a>.</div></dd></dl><dl class="bkr_refwrap"><dt>30.</dt><dd><div class="bk_ref" id="clopidogrel.REF.30">James S., Akerblom A., Cannon C.P., Emanuelsson H., et al. Comparison of ticagrelor, the first reversible oral P2Y(12) receptor antagonist, with clopidogrel in patients with acute coronary syndromes: Rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial. <span><span class="ref-journal">Am Heart J. </span>2009;<span class="ref-vol">157</span>(4):599–605.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19332184" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19332184</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>31.</dt><dd><div class="bk_ref" id="clopidogrel.REF.31">Wallentin L., Becker R.C., Budaj A., Cannon C.P., et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. <span><span class="ref-journal">N Engl J Med. </span>2009;<span class="ref-vol">361</span>(11):1045–57.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19717846" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19717846</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>32.</dt><dd><div class="bk_ref" id="clopidogrel.REF.32">Velders M.A., Abtan J., Angiolillo D.J., Ardissino D., et al. Safety and efficacy of ticagrelor and clopidogrel in primary percutaneous coronary intervention. <span><span class="ref-journal">Heart. </span>2016;<span class="ref-vol">102</span>(8):617–25.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26848185" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26848185</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>33.</dt><dd><div class="bk_ref" id="clopidogrel.REF.33">Moustafa B., Testai F.D. Navigating Antiplatelet Treatment Options for Stroke: Evidence-Based and Pragmatic Strategies. <span><span class="ref-journal">Curr Neurol Neurosci Rep. </span>2022;<span class="ref-vol">22</span>(11):789–802.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/36227497" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36227497</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>34.</dt><dd><div class="bk_ref" id="clopidogrel.REF.34">Li C., Liu M., Chen W., Jiang T., et al. Comparison of ticagrelor and clopidogrel on platelet function and prognosis in unstable angina. <span><span class="ref-journal">Eur J Clin Pharmacol. </span>2022;<span class="ref-vol">78</span>(12):1949–1958.</span> [<a href="/pmc/articles/PMC9649465/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9649465</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36245047" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36245047</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>35.</dt><dd><div class="bk_ref" id="clopidogrel.REF.35">Lin Y., Cai Z., Dong S., Liu H., et al. Comparative efficacy and safety of antiplatelet or anticoagulant therapy in patients with chronic coronary syndromes after percutaneous coronary intervention: A network meta-analysis of randomized controlled trials. <span><span class="ref-journal">Front Pharmacol. </span>2022;<span class="ref-vol">13</span>:992376. </span> p. [<a href="/pmc/articles/PMC9563230/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9563230</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36249742" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36249742</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>36.</dt><dd><div class="bk_ref" id="clopidogrel.REF.36">Saint Croix G., Lacy S.C., Gazzhal A., Ibrahim M., et al. Dual Antiplatelet Therapy in Patients Aged 75 Years and Older with Coronary Artery Disease: A Meta-Analysis and Systematic Review. <span><span class="ref-journal">J Interv Cardiol. </span>2022;<span class="ref-vol">2022</span>:3111840. </span> p. [<a href="/pmc/articles/PMC9499790/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9499790</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36176329" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36176329</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>37.</dt><dd><div class="bk_ref" id="clopidogrel.REF.37">Levine G.N., Bates E.R., Bittl J.A., Brindis R.G., et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. <span><span class="ref-journal">J Thorac Cardiovasc Surg. </span>2016;<span class="ref-vol">152</span>(5):1243–1275.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27751237" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27751237</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>38.</dt><dd><div class="bk_ref" id="clopidogrel.REF.38">Peterson J.F., Field J.R., Unertl K.M., Schildcrout J.S., et al. Physician response to implementation of genotype-tailored antiplatelet therapy. <span><span class="ref-journal">Clin Pharmacol Ther. </span>2016;<span class="ref-vol">100</span>(1):67–74.</span> [<a href="/pmc/articles/PMC4899238/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4899238</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26693963" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26693963</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>39.</dt><dd><div class="bk_ref" id="clopidogrel.REF.39">Mitropoulou C., Fragoulakis V., Rakicevic L.B., Novkovic M.M., et al. Economic analysis of pharmacogenomic-guided clopidogrel treatment in Serbian patients with myocardial infarction undergoing primary percutaneous coronary intervention. <span><span class="ref-journal">Pharmacogenomics. </span>2016</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27767438" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27767438</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>40.</dt><dd><div class="bk_ref" id="clopidogrel.REF.40">Jovanovic L., Antonijevic N., Novakovic T., Savic N., et al. Practical Aspects of Monitoring of Antiplatelet Therapy. <span><span class="ref-journal">Semin Thromb Hemost. </span>2017;<span class="ref-vol">43</span>(1):14–23.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27825182" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27825182</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>41.</dt><dd><div class="bk_ref" id="clopidogrel.REF.41">Silvain J., Lattuca B., Beygui F., Range G., et al. Ticagrelor versus clopidogrel in elective percutaneous coronary intervention (ALPHEUS): a randomised, open-label, phase 3b trial. <span><span class="ref-journal">Lancet. </span>2020;<span class="ref-vol">396</span>(10264):1737–1744.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/33202219" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33202219</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>42.</dt><dd><div class="bk_ref" id="clopidogrel.REF.42">Chan N.C., Eikelboom J.W., Ginsberg J.S., Lauw M.N., et al. Role of phenotypic and genetic testing in managing clopidogrel therapy. <span><span class="ref-journal">Blood. </span>2014;<span class="ref-vol">124</span>(5):689–99.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24951432" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24951432</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>43.</dt><dd><div class="bk_ref" id="clopidogrel.REF.43">Erlinge D., James S., Duvvuru S., Jakubowski J.A., et al. Clopidogrel metaboliser status based on point-of-care CYP2C19 genetic testing in patients with coronary artery disease. <span><span class="ref-journal">Thromb Haemost. </span>2014;<span class="ref-vol">111</span>(5):943–50.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24402637" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24402637</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>44.</dt><dd><div class="bk_ref" id="clopidogrel.REF.44">Cascorbi I., Bruhn O., Werk A.N. Challenges in pharmacogenetics. <span><span class="ref-journal">Eur J Clin Pharmacol. </span>2013;<span class="ref-vol">69</span> Suppl 1:17–23.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23640184" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23640184</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>45.</dt><dd><div class="bk_ref" id="clopidogrel.REF.45">Sorich M.J., Vitry A., Ward M.B., Horowitz J.D., et al. Prasugrel vs. clopidogrel for cytochrome P450 2C19-genotyped subgroups: integration of the TRITON-TIMI 38 trial data. <span><span class="ref-journal">J Thromb Haemost. </span>2010;<span class="ref-vol">8</span>(8):1678–84.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20492467" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20492467</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>46.</dt><dd><div class="bk_ref" id="clopidogrel.REF.46">Damani S.B., Topol E.J. The case for routine genotyping in dual-antiplatelet therapy. <span><span class="ref-journal">J Am Coll Cardiol. </span>2010;<span class="ref-vol">56</span>(2):109–11.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20471193" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20471193</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>47.</dt><dd><div class="bk_ref" id="clopidogrel.REF.47">Moriyama B., Obeng A.O., Barbarino J., Penzak S.R., et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP2C19 and Voriconazole Therapy. <span><span class="ref-journal">Clin Pharmacol Ther. </span>2016</span> [<a href="/pmc/articles/PMC5474211/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5474211</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27981572" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27981572</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>48.</dt><dd><div class="bk_ref" id="clopidogrel.REF.48">dbSNP. <em>rs3758581 RefSNP Report</em>. 14 Oct 2022; Available from: <a href="https://www.ncbi.nlm.nih.gov/snp/rs3758581" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://www<wbr style="display:inline-block"></wbr>​.ncbi.nlm<wbr style="display:inline-block"></wbr>​.nih.gov/snp/rs3758581</a>.</div></dd></dl><dl class="bkr_refwrap"><dt>49.</dt><dd><div class="bk_ref" id="clopidogrel.REF.49">ClinVar. <em>[VCV000039354.3]</em>. 14 Oct 2022; Available from: <a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/VCV000039354.3" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://www<wbr style="display:inline-block"></wbr>​.ncbi.nlm<wbr style="display:inline-block"></wbr>​.nih.gov/clinvar/variation/VCV000039354<wbr style="display:inline-block"></wbr>​.3</a>.</div></dd></dl><dl class="bkr_refwrap"><dt>50.</dt><dd><div class="bk_ref" id="clopidogrel.REF.50">PharmVar. <em>CYP2C19</em>. 14 Oct 2022; Available from: <a href="https://www.pharmvar.org/gene/CYP2C19" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://www<wbr style="display:inline-block"></wbr>​.pharmvar.org/gene/CYP2C19</a>.</div></dd></dl><dl class="bkr_refwrap"><dt>51.</dt><dd><div class="bk_ref" id="clopidogrel.REF.51">CYP2C19 allele functionality table [Cited 30 Sept 2022]. Available from: <a href="https://files.cpicpgx.org/data/report/current/allele_function_reference/CYP2C19_allele_functionality_reference.xlsx" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://files<wbr style="display:inline-block"></wbr>​.cpicpgx<wbr style="display:inline-block"></wbr>​.org/data/report/current<wbr style="display:inline-block"></wbr>​/allele_function_reference<wbr style="display:inline-block"></wbr>​/CYP2C19_allele<wbr style="display:inline-block"></wbr>​_functionality_reference.xlsx</a>.</div></dd></dl><dl class="bkr_refwrap"><dt>52.</dt><dd><div class="bk_ref" id="clopidogrel.REF.52">Alrajeh K.Y., Roman Y.M. The frequency of major CYP2C19 genetic polymorphisms in women of Asian, Native Hawaiian and Pacific Islander subgroups. <span><span class="ref-journal">Per Med. </span>2022;<span class="ref-vol">19</span>(4):327–339.</span> [<a href="/pmc/articles/PMC9318053/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9318053</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35748236" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35748236</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>53.</dt><dd><div class="bk_ref" id="clopidogrel.REF.53">Shuldiner A.R., O'Connell J.R., Bliden K.P., Gandhi A., et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. <span><span class="ref-journal">JAMA. </span>2009;<span class="ref-vol">302</span>(8):849–57.</span> [<a href="/pmc/articles/PMC3641569/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3641569</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19706858" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19706858</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>54.</dt><dd><div class="bk_ref" id="clopidogrel.REF.54">Scott S.A., Sangkuhl K., Stein C.M., Hulot J.S., et al. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. <span><span class="ref-journal">Clin Pharmacol Ther. </span>2013;<span class="ref-vol">94</span>(3):317–23.</span> [<a href="/pmc/articles/PMC3748366/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3748366</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23698643" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23698643</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>55.</dt><dd><div class="bk_ref" id="clopidogrel.REF.55">Pratt V.M., Del Tredici A.L., Hachad H., Ji Y., et al. Recommendations for Clinical CYP2C19 Genotyping Allele Selection: A Report of the Association for Molecular Pathology. <span><span class="ref-journal">J Mol Diagn. </span>2018;<span class="ref-vol">20</span>(3):269–276.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29474986" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29474986</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>56.</dt><dd><div class="bk_ref" id="clopidogrel.REF.56">Gelbenegger G., Jilma B. Clinical pharmacology of antiplatelet drugs. <span><span class="ref-journal">Expert Rev Clin Pharmacol. </span>2022:1–21.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/36065676" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36065676</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>57.</dt><dd><div class="bk_ref" id="clopidogrel.REF.57">Mugosa S., Radosavljevic I., Sahman M., Djordjevic N., et al. Risk factors for adverse drug reactions associated with clopidogrel therapy. <span><span class="ref-journal">Open Med (Wars). </span>2022;<span class="ref-vol">17</span>(1):694–701.</span> [<a href="/pmc/articles/PMC8990878/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8990878</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35480401" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35480401</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>58.</dt><dd><div class="bk_ref" id="clopidogrel.REF.58">Mega J.L., Close S.L., Wiviott S.D., Shen L., et al. Cytochrome p-450 polymorphisms and response to clopidogrel. <span><span class="ref-journal">N Engl J Med. </span>2009;<span class="ref-vol">360</span>(4):354–62.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19106084" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19106084</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>59.</dt><dd><div class="bk_ref" id="clopidogrel.REF.59">Mega J.L., Simon T., Collet J.P. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. <span><span class="ref-journal">JAMA. </span>2010;<span class="ref-vol">304</span>(16):1821–30.</span> J.L. Anderson, et al. p. [<a href="/pmc/articles/PMC3048820/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3048820</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20978260" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20978260</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>60.</dt><dd><div class="bk_ref" id="clopidogrel.REF.60">Simon T., Verstuyft C., Mary-Krause M., Quteineh L., et al. Genetic determinants of response to clopidogrel and cardiovascular events. <span><span class="ref-journal">N Engl J Med. </span>2009;<span class="ref-vol">360</span>(4):363–75.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19106083" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19106083</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>61.</dt><dd><div class="bk_ref" id="clopidogrel.REF.61">Chen Y.W., Liao Y.J., Chang W.C., Hsiao T.H., et al. CYP2C19 loss-of-function alleles predicts clinical outcomes in East Asian patients with acute myocardial infarction undergoing percutaneous coronary intervention and stenting receiving clopidogrel. <span><span class="ref-journal">Front Cardiovasc Med. </span>2022;<span class="ref-vol">9</span>:994184. </span> p. [<a href="/pmc/articles/PMC9441652/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9441652</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36072879" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36072879</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>62.</dt><dd><div class="bk_ref" id="clopidogrel.REF.62">Wang T., Feng J., Zhou L., Zhao T., et al. The Cytochrome P450 2C19 Polymorphism is Associated with Major Adverse Cardiovascular Events Risk in Kazak Patients Undergoing Percutaneous Coronary Intervention and Receiving Clopidogrel. <span><span class="ref-journal">Endocr Metab Immune Disord Drug Targets. </span>2022</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/35616671" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35616671</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>63.</dt><dd><div class="bk_ref" id="clopidogrel.REF.63">Mega J.L., Hochholzer W., Frelinger A.L. 3rd, Kluk M.J., et al. Dosing clopidogrel based on CYP2C19 genotype and the effect on platelet reactivity in patients with stable cardiovascular disease. <span><span class="ref-journal">JAMA. </span>2011;<span class="ref-vol">306</span>(20):2221–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22088980" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22088980</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>64.</dt><dd><div class="bk_ref" id="clopidogrel.REF.64">Carreras E.T., Hochholzer W., Frelinger A.L. 3rd, Nordio F., et al. Diabetes mellitus, CYP2C19 genotype, and response to escalating doses of clopidogrel. Insights from the ELEVATE-TIMI 56 Trial. <span><span class="ref-journal">Thromb Haemost. </span>2016;<span class="ref-vol">116</span>(1):69–77.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27009617" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27009617</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>65.</dt><dd><div class="bk_ref" id="clopidogrel.REF.65">Sheng X.Y., An H.J., He Y.Y., Ye Y.F., et al. High-Dose Clopidogrel versus Ticagrelor in CYP2C19 intermediate or poor metabolizers after percutaneous coronary intervention: A Meta-Analysis of Randomized Trials. <span><span class="ref-journal">J Clin Pharm Ther. </span>2022;<span class="ref-vol">47</span>(8):1112–1121.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/35396752" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35396752</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>66.</dt><dd><div class="bk_ref" id="clopidogrel.REF.66">Bhatt D.L., Pare G., Eikelboom J.W., Simonsen K.L., et al. The relationship between CYP2C19 polymorphisms and ischaemic and bleeding outcomes in stable outpatients: the CHARISMA genetics study. <span><span class="ref-journal">Eur Heart J. </span>2012;<span class="ref-vol">33</span>(17):2143–50.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22450429" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22450429</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>67.</dt><dd><div class="bk_ref" id="clopidogrel.REF.67">Paré G., Mehta S.R., Yusuf S., Anand S.S., et al. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. <span><span class="ref-journal">N Engl J Med. </span>2010;<span class="ref-vol">363</span>(18):1704–14.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20979470" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20979470</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>68.</dt><dd><div class="bk_ref" id="clopidogrel.REF.68">Clopidogrel resistance and clopidogrel treatment failure [Cited 17 July, 2017]. Available from: Clopidogrel resistance and clopidogrel treatment failure.</div></dd></dl><dl class="bkr_refwrap"><dt>69.</dt><dd><div class="bk_ref" id="clopidogrel.REF.69">Yi X., Lin J., Wang Y., Zhou Q., et al. Association of Cytochrome P450 Genetic Variants with Clopidogrel Resistance and Outcomes in Acute Ischemic Stroke. <span><span class="ref-journal">J Atheroscler Thromb. </span>2016;<span class="ref-vol">23</span>(10):1188–1200.</span> [<a href="/pmc/articles/PMC5098919/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5098919</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26961113" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26961113</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>70.</dt><dd><div class="bk_ref" id="clopidogrel.REF.70">Pan Y., Chen W., Xu Y., Yi X., et al. Genetic Polymorphisms and Clopidogrel Efficacy for Acute Ischemic Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis. <span><span class="ref-journal">Circulation. </span>2017;<span class="ref-vol">135</span>(1):21–33.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27806998" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27806998</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>71.</dt><dd><div class="bk_ref" id="clopidogrel.REF.71">Wang Y., Cai H., Zhou G., Zhang Z., et al. Effect of CYP2C19*2 and *3 on clinical outcome in ischemic stroke patients treated with clopidogrel. <span><span class="ref-journal">J Neurol Sci. </span>2016;<span class="ref-vol">369</span>:216–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27653892" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27653892</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>72.</dt><dd><div class="bk_ref" id="clopidogrel.REF.72">McDermott J.H., Leach M., Sen D., Smith C.J., et al. The role of CYP2C19 genotyping to guide antiplatelet therapy following ischemic stroke or transient ischemic attack. <span><span class="ref-journal">Expert Rev Clin Pharmacol. </span>2022;<span class="ref-vol">15</span>(7):811–825.</span> [<a href="/pmc/articles/PMC9612933/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9612933</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35912831" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35912831</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>73.</dt><dd><div class="bk_ref" id="clopidogrel.REF.73">Wang Y., Zhao X., Lin J., Li H., et al. Association Between CYP2C19 Loss-of-Function Allele Status and Efficacy of Clopidogrel for Risk Reduction Among Patients With Minor Stroke or Transient Ischemic Attack. <span><span class="ref-journal">JAMA. </span>2016;<span class="ref-vol">316</span>(1):70–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27348249" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27348249</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>74.</dt><dd><div class="bk_ref" id="clopidogrel.REF.74">Wang Y., Meng X., Wang A., Xie X., et al. Ticagrelor versus Clopidogrel in CYP2C19 Loss-of-Function Carriers with Stroke or TIA. <span><span class="ref-journal">N Engl J Med. </span>2021;<span class="ref-vol">385</span>(27):2520–2530.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/34708996" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34708996</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>75.</dt><dd><div class="bk_ref" id="clopidogrel.REF.75">Hoh B.L., Gong Y., McDonough C.W., Waters M.F., et al. CYP2C19 and CES1 polymorphisms and efficacy of clopidogrel and aspirin dual antiplatelet therapy in patients with symptomatic intracranial atherosclerotic disease. <span><span class="ref-journal">J Neurosurg. </span>2016;<span class="ref-vol">124</span>(6):1746–51.</span> [<a href="/pmc/articles/PMC4915569/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4915569</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26587656" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26587656</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>76.</dt><dd><div class="bk_ref" id="clopidogrel.REF.76">Lee J.H., Ahn S.G., Lee J.W., Youn Y.J., et al. Switching from prasugrel to clopidogrel based on Cytochrome P450 2C19 genotyping in East Asian patients stabilized after acute myocardial infarction. <span><span class="ref-journal">Platelets. </span>2016;<span class="ref-vol">27</span>(4):301–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26556524" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26556524</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>77.</dt><dd><div class="bk_ref" id="clopidogrel.REF.77">Malhotra N., Abunassar J., Wells G.A., McPherson R., et al. A pharmacodynamic comparison of a personalized strategy for anti-platelet therapy versus ticagrelor in achieving a therapeutic window. <span><span class="ref-journal">Int J Cardiol. </span>2015;<span class="ref-vol">197</span>:318–25.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26151596" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26151596</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>78.</dt><dd><div class="bk_ref" id="clopidogrel.REF.78">Roberts J.D., Wells G.A., Le May M.R., Labinaz M., et al. Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial. <span><span class="ref-journal">Lancet. </span>2012;<span class="ref-vol">379</span>(9827):1705–11.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22464343" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22464343</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>79.</dt><dd><div class="bk_ref" id="clopidogrel.REF.79">Jiang M., You J.H. Cost-effectiveness analysis of personalized antiplatelet therapy in patients with acute coronary syndrome. <span><span class="ref-journal">Pharmacogenomics. </span>2016;<span class="ref-vol">17</span>(7):701–13.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27167099" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27167099</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>80.</dt><dd><div class="bk_ref" id="clopidogrel.REF.80">Jiang M., You J.H. CYP2C19 genotype plus platelet reactivity-guided antiplatelet therapy in acute coronary syndrome patients: a decision analysis. <span><span class="ref-journal">Pharmacogenet Genomics. </span>2015;<span class="ref-vol">25</span>(12):609–17.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26398625" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26398625</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>81.</dt><dd><div class="bk_ref" id="clopidogrel.REF.81">Cavallari L.H., Lee C.R., Beitelshees A.L., Cooper-DeHoff R.M., et al. Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention. <span><span class="ref-journal">JACC Cardiovasc Interv. </span>2018</span> [<a href="/pmc/articles/PMC5775044/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5775044</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29102571" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29102571</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>82.</dt><dd><div class="bk_ref" id="clopidogrel.REF.82">Samardzic J., Bozina N., Skoric B., Ganoci L., et al. CYP2C19*2 genotype influence in acute coronary syndrome patients undergoing serial clopidogrel dose tailoring based on platelet function testing: Analysis from randomized controlled trial NCT02096419. <span><span class="ref-journal">Int J Cardiol. </span>2015;<span class="ref-vol">186</span>:282–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25828136" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25828136</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>83.</dt><dd><div class="bk_ref" id="clopidogrel.REF.83">Collet J.P., Hulot J.S., Cuisset T., Range G., et al. Genetic and platelet function testing of antiplatelet therapy for percutaneous coronary intervention: the ARCTIC-GENE study. <span><span class="ref-journal">Eur J Clin Pharmacol. </span>2015;<span class="ref-vol">71</span>(11):1315–24.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26265231" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26265231</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>84.</dt><dd><div class="bk_ref" id="clopidogrel.REF.84">Park M.W., Her S.H., Kim C.J. Evaluation of the incremental prognostic value of the combination of CYP2C19 poor metabolizer status and ABCB1 3435 TT polymorphism over conventional risk factors for cardiovascular events after drug-eluting stent implantation in East Asians. <span><span class="ref-journal">Genet Med. </span>2016;<span class="ref-vol">18</span>(8):833–41.</span> J. SunCho, et al. p. [<a href="https://pubmed.ncbi.nlm.nih.gov/26699760" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26699760</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>85.</dt><dd><div class="bk_ref" id="clopidogrel.REF.85">Kleindorfer D.O., Towfighi A., Chaturvedi S., Cockroft K.M., et al. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association. <span><span class="ref-journal">Stroke. </span>2021;<span class="ref-vol">52</span>(7):e364–e467.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/34024117" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34024117</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>86.</dt><dd><div class="bk_ref" id="clopidogrel.REF.86">Yang Y., Lewis J.P., Hulot J.S., Scott S.A. The pharmacogenetic control of antiplatelet response: candidate genes and CYP2C19. <span><span class="ref-journal">Expert Opin Drug Metab Toxicol. </span>2015;<span class="ref-vol">11</span>(10):1599–1617.</span> [<a href="/pmc/articles/PMC4829114/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4829114</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26173871" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26173871</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>87.</dt><dd><div class="bk_ref" id="clopidogrel.REF.87">Kalman L.V., Agundez J., Appell M.L., Black J.L., et al. Pharmacogenetic allele nomenclature: International workgroup recommendations for test result reporting. <span><span class="ref-journal">Clin Pharmacol Ther. </span>2016;<span class="ref-vol">99</span>(2):172–85.</span> [<a href="/pmc/articles/PMC4724253/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4724253</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26479518" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26479518</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>88.</dt><dd><div class="bk_ref" id="clopidogrel.REF.88">den Dunnen, J.T., R.
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Dalgleish, D.R.
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Maglott, R.K.
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Hart, et al. <span class="ref-title">HGVS Recommendations for the Description of Sequence Variants: 2016 Update. </span><span class="ref-journal">Hum Mutat</span>, 2016.37(6): p.564-9.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/26931183" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26931183</span></a>]</div></dd></dl></dl></div><h2 id="NBK84114_footnotes">Footnotes</h2><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>
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<sup>1</sup>
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</dt><dd><div id="clopidogrel.FN1"><p class="no_top_margin"> The FDA labels specific drug formulations. We have substituted the generic names for any drug labels in this excerpt. The FDA may not have labeled all formulations containing the generic drug. Certain terms, genes and genetic variants may be corrected in accordance to nomenclature standards, where necessary. We have given the full name of abbreviations, shown in square brackets, where necessary.</p></div></dd></dl></dl><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK84114_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><p class="contrib-group"><h4>Authors</h4><span itemprop="author">Laura Dean</span>, MD<sup>1</sup> and <span itemprop="author">Megan Kane</span>, PhD<sup><img src="/corehtml/pmc/pmcgifs/corrauth.gif" alt="corresponding author" /></sup><sup>2</sup>.</p><h4>Affiliations</h4><div class="affiliation"><sup>1</sup> NCBI<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="vog.hin.mln.ibcn@sgm" class="oemail">vog.hin.mln.ibcn@sgm</a></div></div><div class="affiliation"><sup>2</sup> NCBI<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="vog.hin.mln.ibcn@sgm" class="oemail">vog.hin.mln.ibcn@sgm</a></div></div><div><sup><img src="/corehtml/pmc/pmcgifs/corrauth.gif" alt="corresponding author" /></sup>Corresponding author.</div><h3>Publication History</h3><p class="small">Created: <span itemprop="datePublished">March 8, 2012</span>; Last Update: <span itemprop="dateModified">December 1, 2022</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a><p class="small">All Medical Genetics Summaries content, except where otherwise noted, is licensed under a Creative Commons <a href="https://creativecommons.org/licenses/by/4.0/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">Attribution 4.0 International (CC BY 4.0)</a> license which permits copying, distribution, and adaptation of the work, provided the original work is properly cited and any changes from the original work are properly indicated. Any altered, transformed, or adapted form of the work may only be distributed under the same or similar license to this one.</p></div></div><h3>Publisher</h3><p><a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=books" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Center for Biotechnology Information (US)</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>Dean L, Kane M. Clopidogrel Therapy and CYP2C19 Genotype. 2012 Mar 8 [Updated 2022 Dec 1]. In: Pratt VM, Scott SA, Pirmohamed M, et al., editors. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012-. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/gtrbook/clobazam/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gtrbook/clozapine/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobclopidogrelTthefda2022druglabelfo"><div id="clopidogrel.T.the_fda_2022_drug_label_fo" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>The FDA (2022) Drug Label for Clopidogrel. Warning: Diminished Antiplatelet Effect in Individuals with 2 Loss-of-Function Alleles of the <i>CYP2C19</i> Gene.</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK84114/table/clopidogrel.T.the_fda_2022_drug_label_fo/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__clopidogrel.T.the_fda_2022_drug_label_fo_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_clopidogrel.T.the_fda_2022_drug_label_fo_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Phenotype</th><th id="hd_h_clopidogrel.T.the_fda_2022_drug_label_fo_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Recommendations</th></tr></thead><tbody><tr><td headers="hd_h_clopidogrel.T.the_fda_2022_drug_label_fo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CYP2C19 poor metabolizer</td><td headers="hd_h_clopidogrel.T.the_fda_2022_drug_label_fo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Clopidogrel bisulfate at recommended doses forms less of the active metabolite and so has a reduced effect on platelet activity in individuals who are homozygous for no-function alleles of the <i>CYP2C19</i> gene, (termed "CYP2C19 poor metabolizers"). Tests are available to identify individuals who are CYP2C19 poor metabolizers. Consider use of another platelet P2Y12 inhibitor in individuals identified as CYP2C19 poor metabolizers</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">Please see <a href="#clopidogrel.Therapeutic_Recommendations">Therapeutic Recommendations based on Genotype</a> for more information from the FDA. This table is adapted from (<a class="bibr" href="#clopidogrel.REF.1" rid="clopidogrel.REF.1">1</a>).</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobclopidogrelTthecpic2022antiplatelet"><div id="clopidogrel.T.the_cpic_2022_antiplatelet" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>The CPIC (2022) Antiplatelet Therapy Recommendations based on CYP2C19 Phenotype when considering Clopidogrel for Cardiovascular Indications.</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK84114/table/clopidogrel.T.the_cpic_2022_antiplatelet/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__clopidogrel.T.the_cpic_2022_antiplatelet_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Phenotype</th><th id="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Examples of diplotypes</th><th id="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Implications for clopidogrel</th><th id="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Therapeutic recommendations</th><th id="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Classification of recommendation- ACS, or PCI<sup>a</sup>, or both</th><th id="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_6" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Classification of recommendation, non-ACS, non-PCI cardiovascular indications<sup>b</sup></th></tr></thead><tbody><tr><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ultrarapid metabolizer (UM)</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<i>*17/*17</i>
|
|
</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Increased clopidogrel active metabolite formation; lower on-treatment platelet reactivity; no association with higher bleeding risk</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_4" rowspan="2" colspan="1" style="text-align:left;vertical-align:top;">If considering clopidogrel, use at standard dose (75 mg/day)</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_5" rowspan="2" colspan="1" style="text-align:left;vertical-align:top;">Strong</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_6" rowspan="2" colspan="1" style="text-align:left;vertical-align:top;">No recommendation</td></tr><tr><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Rapid metabolizer (RM)</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<i>*1/*17</i>
|
|
</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Normal or increased clopidogrel active metabolite formation; normal or lower on-treatment platelet reactivity; no association with higher bleeding risk</td></tr><tr><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Normal metabolizer (NM)</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<i>*1/*1</i>
|
|
<br />
|
|
<i>*1/*13</i>
|
|
</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Normal clopidogrel active metabolite formation; normal on-treatment platelet reactivity</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">If considering clopidogrel, use at standard dose (75 mg/day)</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Strong</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Strong</td></tr><tr><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Likely intermediate metabolizer</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<i>*1/*9</i>
|
|
<br />
|
|
<i>*1/*16</i>
|
|
<br />
|
|
<i>*1/*10</i>
|
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</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Avoid standard-dose clopidogrel (75 mg/day) if possible. Use prasugrel or ticagrelor at standard dose if no contraindication</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Strong<sup>c</sup></td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No recommendation<sup>c</sup></td></tr><tr><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intermediate metabolizer (IM)</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<i>*1/*2</i>
|
|
<br />
|
|
<i>*1/*3</i>
|
|
<br />
|
|
<i>*2/*17</i>
|
|
</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Avoid standard-dose (75 mg/day) clopidogrel if possible. Use prasugrel or ticagrelor at standard dose if no contraindication</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Strong</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No recommendation</td></tr><tr><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Likely poor metabolizer</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<i>*2/*9</i>
|
|
<br />
|
|
<i>*3/*19</i>
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|
<br />
|
|
<i>*4/*10</i>
|
|
</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Significantly reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Avoid clopidogrel if possible. Use prasugrel or ticagrelor at standard dose if no contraindication</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Strong<sup>c</sup></td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate<sup>c</sup></td></tr><tr><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Poor metabolizer (PM)</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<i>*2/*2</i>
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|
<br />
|
|
<i>*2/*3</i>
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|
<br />
|
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<i>*3/*3</i>
|
|
</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Significantly reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Avoid clopidogrel if possible. Use prasugrel or ticagrelor at standard dose if no contraindication</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Strong</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt><sup>a</sup>
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</dt><dd><div id="clopidogrel.TF.2.1"><p class="no_margin">ACS or PCI, or both includes individuals undergoing PCI for an ACS or non-ACS (elective) indication.</p></div></dd></dl><dl class="bkr_refwrap"><dt><sup>b</sup>
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</dt><dd><div id="clopidogrel.TF.2.2"><p class="no_margin">Non-ACS, non-PCI cardiovascular indications include peripheral arterial disease and stable coronary artery disease following a recent myocardial infarction outside the setting of PCI.</p></div></dd></dl><dl class="bkr_refwrap"><dt><sup>c</sup>
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|
</dt><dd><div id="clopidogrel.TF.2.3"><p class="no_margin">The strength of the recommendation for “likely” phenotypes are the same as their respective confirmed phenotypes; “likely” indicates the uncertainty in phenotype assignment due to limited data for reduced-function alleles.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ACS - acute coronary syndrome; PCI - percutaneous coronary intervention; CPIC - Clinical Pharmacogenetics Implementation Consortium</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Please see Therapeutic Recommendations based on Genotype for more information from CPIC. This table is adapted from (<a class="bibr" href="#clopidogrel.REF.3" rid="clopidogrel.REF.3">3</a>).</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobclopidogrelTthecpic2022antiplatelet1"><div id="clopidogrel.T.the_cpic_2022_antiplatelet_1" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>The CPIC (2022) Antiplatelet Therapy Recommendations Based on CYP2C19 Phenotype when Considering Clopidogrel for Neurovascular<sup>a</sup> Indications</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK84114/table/clopidogrel.T.the_cpic_2022_antiplatelet_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__clopidogrel.T.the_cpic_2022_antiplatelet_1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CYP2C19 phenotype</th><th id="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Implications for clopidogrel</th><th id="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Therapeutic recommendation</th><th id="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Classification of recommendation<sup>b</sup></th></tr></thead><tbody><tr><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ultrarapid metabolizer (UM)</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Increased clopidogrel active metabolite formation; lower on-treatment platelet reactivity; no association with higher bleeding risk</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:top;">No recommendation</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_4" rowspan="2" colspan="1" style="text-align:left;vertical-align:top;">No recommendation</td></tr><tr><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Rapid metabolizer (RM)</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Normal or increased clopidogrel active metabolite formation; normal or lower on-treatment platelet reactivity; no association with higher bleeding risk</td></tr><tr><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Normal metabolizer (NM)</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Normal clopidogrel active metabolite formation; normal on-treatment platelet reactivity</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">If considering clopidogrel, use at standard dose (75 mg/day)</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Strong</td></tr><tr><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Likely and confirmed intermediate metabolizer (IM)</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Consider an alternative<sup>c</sup> P2Y12 inhibitor at standard dose if clinically indicated and no contraindication</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate</td></tr><tr><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Likely and confirmed poor metabolizer (PM)</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Significantly reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Avoid clopidogrel if possible.<br />Consider an alternative<sup>c</sup> P2Y12 inhibitor at standard dose if clinically indicated and no contraindication</td><td headers="hd_h_clopidogrel.T.the_cpic_2022_antiplatelet_1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt><sup>a</sup>
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|
</dt><dd><div id="clopidogrel.TF.3.1"><p class="no_margin">Neurovascular disease includes acute ischemic stroke or transient ischemic attack (TIA), secondary prevention of stroke, or prevention of thromboembolic events following neurointerventional procedures, such as carotid artery stenting and stent-assisted coiling of intracranial aneurysms.</p></div></dd></dl><dl class="bkr_refwrap"><dt><sup>b</sup>
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|
</dt><dd><div id="clopidogrel.TF.3.2"><p class="no_margin">The strength of the recommendation for “likely” phenotypes are the same as their respective confirmed phenotypes; “likely” indicates the uncertainty in phenotype assignment due to limited data for reduced function alleles.</p></div></dd></dl><dl class="bkr_refwrap"><dt><sup>c</sup>
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|
</dt><dd><div id="clopidogrel.TF.3.3"><p class="no_margin">Alternative P2Y12 inhibitors not impacted by CYP2C19 genetic variants include ticagrelor and ticlopidine. Prasugrel is contraindicated in individuals with a history of stroke or TIA. Given limited outcomes data for genotype-guided antiplatelet therapy for neurovascular indications, selection of therapy should depend on the individual’s treatment goals and risks for adverse events.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Please see Therapeutic Recommendations based on Genotype for more information from CPIC. This table is adapted from (<a class="bibr" href="#clopidogrel.REF.3" rid="clopidogrel.REF.3">3</a>). CPIC - Clinical Pharmacogenetics Implementation Consortium</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobclopidogrelTthedpwg2019recommendati"><div id="clopidogrel.T.the_dpwg_2019_recommendati" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>The DPWG (2019) Recommendations for Clopidogrel and <i>CYP2C19</i> Phenotype.</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK84114/table/clopidogrel.T.the_dpwg_2019_recommendati/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__clopidogrel.T.the_dpwg_2019_recommendati_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_clopidogrel.T.the_dpwg_2019_recommendati_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Phenotype</th><th id="hd_h_clopidogrel.T.the_dpwg_2019_recommendati_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Recommendation</th></tr></thead><tbody><tr><td headers="hd_h_clopidogrel.T.the_dpwg_2019_recommendati_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ultrarapid metabolizer</td><td headers="hd_h_clopidogrel.T.the_dpwg_2019_recommendati_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NO action is required for this gene-drug interaction</td></tr><tr><td headers="hd_h_clopidogrel.T.the_dpwg_2019_recommendati_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intermediate metabolizer</td><td headers="hd_h_clopidogrel.T.the_dpwg_2019_recommendati_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Percutaneous coronary intervention, stroke, or TIA:
|
|
<dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><p class="no_top_margin">choose an alternative or double the dose to 150 mg/day (600 mg loading dose)</p></dd></dl></dl>
|
|
Prasugrel, ticagrelor, and acetylsalicylic acid/dipyridamole are not metabolized by CYP2C19 (or to a lesser extent)<br />Other indications:
|
|
<dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><p class="no_top_margin">no action required</p></dd></dl></dl></td></tr><tr><td headers="hd_h_clopidogrel.T.the_dpwg_2019_recommendati_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Poor metabolizer</td><td headers="hd_h_clopidogrel.T.the_dpwg_2019_recommendati_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Percutaneous coronary intervention, stroke, or TIA:
|
|
<dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><p class="no_top_margin">Avoid clopidogrel</p></dd></dl></dl>
|
|
Prasugrel, ticagrelor, and acetylsalicylic acid/dipyridamole are not metabolized by CYP2C19 (or to a lesser extent)<br />Other indications:
|
|
<dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><p class="no_top_margin">determine the level of inhibition of platelet aggregation by clopidogrel</p></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><p class="no_top_margin">consider an alternative in poor responders</p></dd></dl></dl>
|
|
Prasugrel and ticagrelor are not metabolized by CYP2C19 (or to a lesser extent)</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">TIA - Transient ischemic attack; DPWG – Dutch Pharmacogenetics Working Group</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Please see Therapeutic Recommendations based on Genotype for more information from DPWG. This table is adapted from (<a class="bibr" href="#clopidogrel.REF.4" rid="clopidogrel.REF.4">4</a>).</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobclopidogrelTactivitystatusofselecte"><div id="clopidogrel.T.activity_status_of_selecte" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Activity Status of Selected <i>CYP2C19</i> Alleles</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK84114/table/clopidogrel.T.activity_status_of_selecte/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__clopidogrel.T.activity_status_of_selecte_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_clopidogrel.T.activity_status_of_selecte_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Allele type</th><th id="hd_h_clopidogrel.T.activity_status_of_selecte_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Alleles</th></tr></thead><tbody><tr><td headers="hd_h_clopidogrel.T.activity_status_of_selecte_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Increased function</td><td headers="hd_h_clopidogrel.T.activity_status_of_selecte_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<i>CYP2C19*17</i>
|
|
</td></tr><tr><td headers="hd_h_clopidogrel.T.activity_status_of_selecte_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Normal function</td><td headers="hd_h_clopidogrel.T.activity_status_of_selecte_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<i>CYP2C19*1</i>
|
|
<br />
|
|
<i>CYP2C19*13</i>
|
|
</td></tr><tr><td headers="hd_h_clopidogrel.T.activity_status_of_selecte_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Decreased function^</td><td headers="hd_h_clopidogrel.T.activity_status_of_selecte_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<i>CYP2C19*9</i>
|
|
<br />
|
|
<i>CYP2C19*10</i>
|
|
<br />
|
|
<i>CYP2C19*16</i>
|
|
<br />
|
|
<i>CYP2C19*19</i>
|
|
</td></tr><tr><td headers="hd_h_clopidogrel.T.activity_status_of_selecte_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No function</td><td headers="hd_h_clopidogrel.T.activity_status_of_selecte_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<i>CYP2C19*2</i>
|
|
<br />
|
|
<i>CYP2C19*3</i>
|
|
<br />
|
|
<p>
|
|
<i>CY</i>
|
|
<i>P2C19*4</i>
|
|
</p>
|
|
</td></tr><tr><td headers="hd_h_clopidogrel.T.activity_status_of_selecte_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Uncertain function</td><td headers="hd_h_clopidogrel.T.activity_status_of_selecte_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<i>CYP2C19*12</i>
|
|
<br />
|
|
<i>CYP2C19*23</i>
|
|
</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">This table is adapted from (<a class="bibr" href="#clopidogrel.REF.51" rid="clopidogrel.REF.51">51</a>).</p></div></dd></dl><dl class="bkr_refwrap"><dt>^</dt><dd><div id="clopidogrel.TF.5.1"><p class="no_margin">Note: the evidence supporting the activity status of decreased function alleles is limited.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobclopidogrelTe"><div id="clopidogrel.Te" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK84114/table/clopidogrel.Te/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__clopidogrel.Te_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_clopidogrel.Te_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_clopidogrel.Te_1_1_1_1" style="text-align:left;vertical-align:top;">Common allele name</th><th id="hd_h_clopidogrel.Te_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_clopidogrel.Te_1_1_1_2" style="text-align:left;vertical-align:top;">Alternative names</th><th id="hd_h_clopidogrel.Te_1_1_1_3" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:top;">HGVS reference sequence</th><th id="hd_h_clopidogrel.Te_1_1_1_4" rowspan="2" scope="col" colspan="1" headers="hd_h_clopidogrel.Te_1_1_1_4" style="text-align:left;vertical-align:top;">dbSNP reference identifier for allele location</th></tr><tr><th headers="hd_h_clopidogrel.Te_1_1_1_3" id="hd_h_clopidogrel.Te_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:top;">Coding</th><th headers="hd_h_clopidogrel.Te_1_1_1_3" id="hd_h_clopidogrel.Te_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Protein</th></tr></thead><tbody><tr><td headers="hd_h_clopidogrel.Te_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>CYP2C19*2</i>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">12662A>G</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/633856/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000769.4:c.332-23A>G</a>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<u>(Splicing defect)</u>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/snp/rs12769205" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs12769205</a>
|
|
</td></tr><tr><td headers="hd_h_clopidogrel.Te_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:top;">19154G>A</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/16897/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000769.4:c.681G>A</a>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<u><a href="/protein/4503219/?report=GenPept" class="bk_tag" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=genpept">NP_000760.1</a>:p.</u>
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/16897/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Pro227</a>
|
|
<u>=</u>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/snp/rs4244285" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs4244285</a>
|
|
</td></tr><tr><td headers="hd_h_clopidogrel.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<i>CYP2C19*3</i>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">17948G>A</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/16899/?oq=((31938%5BAlleleID%5D))&m=CYP2C19*3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000769.4:c.636G>A</a>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/16899/?oq=((31938%5BAlleleID%5D))&m=CYP2C19*3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000760.1:p.Trp212Ter</a>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/snp/rs4986893" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs4986893</a>
|
|
</td></tr><tr><td headers="hd_h_clopidogrel.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<i>CYP2C19*4</i>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1A>G</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/16900" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000769.4:c.1A>G</a>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/16900" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000760.1:p.Met1Val</a>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/snp/rs28399504" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs28399504</a>
|
|
</td></tr><tr><td headers="hd_h_clopidogrel.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<i>CYP2C19*9</i>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">12784G>A</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/39352/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000769.4:c.431G>A</a>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/39352/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000760.1:p.Arg144His</a>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/snp/rs17884712" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs17884712</a>
|
|
</td></tr><tr><td headers="hd_h_clopidogrel.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<i>CYP2C19*10</i>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">19153C>T</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/39353/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000769.4:c.680C>T</a>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/39353/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000760.1:p.Pro227Leu</a>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/snp/rs6413438" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs6413438</a>
|
|
</td></tr><tr><td headers="hd_h_clopidogrel.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<i>CYP2C19*12</i>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">90209A>C</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/633853/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000769.4:c.1473A>C</a>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/633853/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000760.1:p.Ter491Cys</a>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/snp/rs55640102" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs55640102</a>
|
|
</td></tr><tr><td headers="hd_h_clopidogrel.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<i>CYP2C19*13</i>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">87290C>T</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/633846/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000769.4:c.1228C>T</a>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/633846/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000760.1:p.Arg410Cys</a>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/snp/rs17879685" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs17879685</a>
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</td></tr><tr><td headers="hd_h_clopidogrel.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<i>CYP2C19*16</i>
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<sup>a</sup>
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</td><td headers="hd_h_clopidogrel.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">90060C>T</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/633849" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000769.4:c.1324C>T</a>
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</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/633849" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000760.1:p.Arg442Cys</a>
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|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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|
<a href="https://www.ncbi.nlm.nih.gov/snp/rs192154563" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs192154563</a>
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|
</td></tr><tr><td headers="hd_h_clopidogrel.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<i>CYP2C19*17</i>
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|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-806C>T</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/39357/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000769.4:c.-806C>T</a>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(Variant alters mRNA expression)</td><td headers="hd_h_clopidogrel.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/snp/rs12248560" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs12248560</a>
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</td></tr><tr><td headers="hd_h_clopidogrel.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<i>CYP2C19*19</i>
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|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">151A>G</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/633933/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000769.4:c.151A>G</a>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/633933/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000760.1:p.Ser51Gly</a>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/snp/rs1564657013" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs1564657013</a>
|
|
</td></tr><tr><td headers="hd_h_clopidogrel.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<i>CYP2C19*23</i>
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|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">12455G>C</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/634042/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000769.4:c.271G>C</a>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_3 hd_h_clopidogrel.Te_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/variation/634042/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000760.1:p.Gly91Arg</a>
|
|
</td><td headers="hd_h_clopidogrel.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/snp/rs118203756" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs118203756</a>
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</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">Note: the normal “wild type” allele is <i>CYP2C19*1</i> and is reported when no variant is detected. The wild type allele is characterized by the common A>G variant at <a href="https://www.ncbi.nlm.nih.gov/snp/rs3758581" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs3758581</a> (<a href="/nuccore/1464923610" class="bk_tag" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=nuccore">NM_000769.4</a>:c.991A>G; <i>CYP2C19</i> p.Ile331Val), which is benign and is found in many <i>CYP2C19</i> haplotypes.</p></div></dd></dl><dl class="bkr_refwrap"><dt><sup>a</sup>
|
|
</dt><dd><div id="clopidogrel.TF.e.1"><p class="no_margin">This allele does not have the A>G variant at <a href="https://www.ncbi.nlm.nih.gov/snp/rs3758581" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs3758581</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Pharmacogenetic Allele Nomenclature: International Workgroup Recommendations for Test Result Reporting (<a class="bibr" href="#clopidogrel.REF.87" rid="clopidogrel.REF.87">87</a>).</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Guidelines for the description and nomenclature of gene variations are available from the Human Genome Variation Society (HGVS (<a class="bibr" href="#clopidogrel.REF.88" rid="clopidogrel.REF.88">88</a>)).</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Nomenclature for cytochrome P450 enzymes is available from Pharmacogene Variation (<a href="http://www.pharmvar.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PharmVar</a>) Consortium.</p></div></dd></dl></dl></div></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><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script></div></div>
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