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<meta name="description" content="There is little evidence available to evaluate the efficacy of buflomedil for IC. Most trials were excluded due to poor quality. The two included trials showed moderately positive results; these are undermined by publication bias since we know of at least another four unpublished, irretrievable, and …"><meta name="keywords" content="pmid:23543509, PMC7047040, doi:10.1002/14651858.CD000988.pub4, Research Support, Non-U.S. Gov&#x27;t, Review, Systematic Review, Tine L M de Backer, Robert Vander Stichele, Administration, Oral, Double-Blind Method, Humans, Intermittent Claudication / drug therapy*, Publication Bias, Pyrrolidines / therapeutic use*, Randomized Controlled Trials as Topic, Treatment Outcome, Vasodilator Agents / therapeutic use*, PubMed Abstract, NIH, NLM, NCBI, National Institutes of Health, National Center for Biotechnology Information, National Library of Medicine, MEDLINE"><meta name="robots" content="index,nofollow,noarchive"><meta property="og:title" content="Buflomedil for intermittent claudication - PubMed"><meta property="og:url" content="https://pubmed.ncbi.nlm.nih.gov/23543509/"><meta property="og:description" content="There is little evidence available to evaluate the efficacy of buflomedil for IC. Most trials were excluded due to poor quality. The two included trials showed moderately positive results; these are undermined by publication bias since we know of at least another four unpublished, irretrievable, and …"><meta property="og:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:image:secure_url" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:type" content="website"><meta property="og:site_name" content="PubMed"><meta name="twitter:domain" content="pubmed.ncbi.nlm.nih.gov"><meta name="twitter:card" content="summary_large_image"><meta name="twitter:title" content="Buflomedil for intermittent claudication - PubMed"><meta name="twitter:url" content="https://pubmed.ncbi.nlm.nih.gov/23543509/"><meta name="twitter:description" content="There is little evidence available to evaluate the efficacy of buflomedil for IC. Most trials were excluded due to poor quality. The two included trials showed moderately positive results; these are undermined by publication bias since we know of at least another four unpublished, irretrievable, and …"><meta name="twitter:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg">
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<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="6TDZzCF5BvS1E2Ia6cnG79WpGSXnEr8cnGn4cs8rb6FvytO0Jv0IBhs3eWFzx2Gw">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="6TDZzCF5BvS1E2Ia6cnG79WpGSXnEr8cnGn4cs8rb6FvytO0Jv0IBhs3eWFzx2Gw">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="6TDZzCF5BvS1E2Ia6cnG79WpGSXnEr8cnGn4cs8rb6FvytO0Jv0IBhs3eWFzx2Gw">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="6TDZzCF5BvS1E2Ia6cnG79WpGSXnEr8cnGn4cs8rb6FvytO0Jv0IBhs3eWFzx2Gw">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="6TDZzCF5BvS1E2Ia6cnG79WpGSXnEr8cnGn4cs8rb6FvytO0Jv0IBhs3eWFzx2Gw">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="23543509">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://doi.org/10.1002/14651858.CD000988.pub4"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3058&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=23543509&amp;db=pubmed&amp;nlmid=100909747"
title="See full text options at Wiley"
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data-ga-action="Wiley"
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><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-7331-42-Cochrane_Library_Logo_RGB_120x30.jpg" alt="Wiley full text link"><span class="text">
Wiley
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/23543509/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=23543509&amp;db=pubmed&amp;nlmid=100909747"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="23543509"
><span class="text">
Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/23543509/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/23543509/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="23543509" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F23543509%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="6TDZzCF5BvS1E2Ia6cnG79WpGSXnEr8cnGn4cs8rb6FvytO0Jv0IBhs3eWFzx2Gw"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
id="collections-action-dialog-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="collections_button"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
Choose a collection:
</label><select id="collections-action-dialog-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
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Background:
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Intermittent claudication (IC) is pain caused by chronic occlusive arterial disease, that develops in a limb during exercise and is relieved with rest. Buflomedil is a vasoactive agent used to treat peripheral vascular disease. However, its clinical efficacy for IC has not yet been critically examined. This is an update of a Cochrane review first published in 2000, and previously updated in 2007 and 2008.
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To evaluate the available evidence on the efficacy of buflomedil for IC.
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For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched January 2013) and CENTRAL (2012, Issue 12).
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Selection criteria:
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Double-blinded, randomized controlled trials (RCTs) in patients with IC (Fontaine stage II) receiving oral buflomedil compared with placebo. Pain-free walking distance (PFWD) and maximum walking distance (MWD) were analysed by standardized exercise test.
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We included two RCTs with 127 participants. Both RCTs showed moderate improvements in PFWD for patients on buflomedil. This improvement was statistically significant for both trials (WMD 75.1 m, 95% confidence interval (CI) 20.6 to 129.6; WMD 80.6 m, 95% CI 3.0 to 158.2), the latter being a wholly diabetic population. For both RCTs, MWD gains were statistically significant with wide confidence intervals (WMD 80.7 m, 95% CI 9.4 to 152; WMD 171.4 m, 95% CI 51.3 to 291.5), respectively.
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There is little evidence available to evaluate the efficacy of buflomedil for IC. Most trials were excluded due to poor quality. The two included trials showed moderately positive results; these are undermined by publication bias since we know of at least another four unpublished, irretrievable, and inconclusive studies.Buflomedil's benefit is small in relation to safety issues and its narrow therapeutic range.
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<p> 1.1. Analysis </p>
</strong>
<div class="figure-caption-contents"><p> Comparison 1 Buflomedil versus placebo,… </p></div>
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<p> 1.1. Analysis </p>
</strong>
<div class="figure-caption-contents"><p> Comparison 1 Buflomedil versus placebo, Outcome 1 Painfree walking distance. Meters gain. </p></div>
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1.1. Analysis
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<div class="figure-caption-contents">Comparison 1 Buflomedil versus placebo, Outcome 1 Painfree walking distance. Meters gain.</div>
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<p> 1.2. Analysis </p>
</strong>
<div class="figure-caption-contents"><p> Comparison 1 Buflomedil versus placebo,… </p></div>
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<p> 1.2. Analysis </p>
</strong>
<div class="figure-caption-contents"><p> Comparison 1 Buflomedil versus placebo, Outcome 2 Maximal walking distance. Meters gain. </p></div>
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<figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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1.2. Analysis
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<div class="figure-caption-contents">Comparison 1 Buflomedil versus placebo, Outcome 2 Maximal walking distance. Meters gain.</div>
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References
</h2>
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<h4 class="refs-list-title">References to studies included in this review</h4>
<div class="refs-list">
<h5 class="refs-list-title">Diamantopoulos 2001 {published data only}</h5>
<ol id="top-references-list-2" class="references-list">
<li>
<ol class="references-and-notes-list">
<li
class="skip-numbering"
value="1">
Diamantopoulos EJ, Grigoriadou M, Ifanti G, Raptis SA. Clinical and hemorheological effects of buflomedil in diabetic subjects with intermittent claudication. International Angiology 2001;20(4):33744.
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<li
class="skip-numbering"
value="1">
Diamantopoulos EJ, Raptis SA, ChristodoulouPeters M, Moulopoulos SD. Controlled trial of buflomedil in diabetic peripheral occlusive disease. Ischaemic Diseases and the Microcirculation. New Results. International Symposium. Frankfurt, January 1989:804.
</li>
</ol>
</li>
</ol>
</div>
<div class="refs-list">
<h5 class="refs-list-title">Trübestein 1984 {published data only}</h5>
<ol id="top-references-list-3" class="references-list">
<li>
<ol class="references-and-notes-list">
<li
class="skip-numbering"
value="1">
Trubestein G, Balzer K, Bisler H, Kluken N, Mahfoud Y, MullerWiefel H, et al. Buflomedil in obstructive arterial disease: Results of a controlled trial [Buflomedil bei arterieller Verschlusskrankheit: Ergebnissse einer kontrollierten Studie]. Deutsche Medizinische Wochenschrift 1982;107(5152):195761.
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class="skip-numbering"
value="1">
Trübestein G, Balzer K, Bisler H, Klüken N, MullerWiefel H, Unkel B, et al. Buflomedil in arterial occlusive disease: results of a controlled multicenter study. Angiology 1984;35(8):5005.
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PubMed
</a>
</li>
</ol>
</li>
</ol>
</div>
</div>
<div class="refs-list">
<h4 class="refs-list-title">References to studies excluded from this review</h4>
<div class="refs-list">
<h5 class="refs-list-title">Bisler 1983 {published data only}</h5>
<ol id="top-references-list-5" class="references-list">
<li>
<ol class="references-and-notes-list">
<li
class="skip-numbering"
value="1">
Bisler H. Clinical response to buflomedil in arterial occlusive disease. Therapiewoche 1983;33:220410.
</li>
</ol>
</li>
</ol>
</div>
<div class="refs-list">
<h5 class="refs-list-title">Fonseca 1988 {published data only}</h5>
<ol id="top-references-list-6" class="references-list">
<li>
<ol class="references-and-notes-list">
<li
class="skip-numbering"
value="1">
Fonseca V, Mikhaildis DP, Barradas MA, Jeremy JY, Gracey L, Dandona P. Doubleblind placebocontrolled trial of buflomedil in intermittent claudication. International Journal of Clinical Pharmacology Research 1988;8(5):37781.
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href="/3229875/"
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data-ga-category="reference"
data-ga-action="3229875"
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PubMed
</a>
</li>
</ol>
</li>
</ol>
</div>
<div class="refs-list">
<h5 class="refs-list-title">Levien 1983 {published data only (unpublished sought but not used)}</h5>
<ol id="top-references-list-7" class="references-list">
<li>
<ol class="references-and-notes-list">
<li
class="skip-numbering"
value="1">
Levien. [Unpublished study] W80BU004LJL. SAfrica, 1983. Mentioned in: Walker GA, Mac Hannaford JC. A metaanalysis of randomized, doubleblind, placebocontrolled studies of the effect of buflomedil on intermittent claudication. Fundamental and Clinical Pharmacology 1995;9(4):38794.
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<a
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PubMed
</a>
</li>
</ol>
</li>
</ol>
</div>
<div class="refs-list">
<h5 class="refs-list-title">Limbs 2008 {published data only}</h5>
<ol id="top-references-list-8" class="references-list">
<li>
<ol class="references-and-notes-list">
<li
class="skip-numbering"
value="1">
Leizorovicz A. Buflomedil reduces amputations in patients with peripheral arterial occlusive disease. American College of Cardiology, 54th Annual Scientific Session, LateBreaking Clinical Trials; 2005 Mar 69; Orlando, Florida 2005.
</li>
</ol>
</li>
<li>
<ol class="references-and-notes-list">
<li
class="skip-numbering"
value="1">
Limbs International Medicinal Buflomedil (LIMB) Study Group, Leizorovicz, A, Becker F. Oral buflomedil in the prevention of cardiovascular events in patients with peripheral arterial obstructive disease: a randomized, placebocontrolled, 4year study.[see comment]. Circulation 2008;117(6):81622.
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PubMed
</a>
</li>
</ol>
</li>
</ol>
</div>
<div class="refs-list">
<h5 class="refs-list-title">Lowe 1987 {unpublished data only}</h5>
<ol id="top-references-list-9" class="references-list">
<li>
<ol class="references-and-notes-list">
<li
class="skip-numbering"
value="1">
Lowe GDO, Dandona P, Horrocks M, Cotton LT. [Unpublished study] Evaluation of the clinical efficacy and safety of oral buflomedil hydrochloride in the treatment of intermittent claudication. Study QL/UK.83/25. UK, 1987. Mentioned in: Walker GA, Mac Hannaford JC. A metaanalysis of randomized, doubleblind, placebocontrolled studies of the effect of buflomedil on intermittent claudication. Fundamental and Clinical Pharmacology 1995;9(4):38794 (Available from the authors).
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PubMed
</a>
</li>
</ol>
</li>
</ol>
</div>
<div class="refs-list">
<h5 class="refs-list-title">Lund 1988 {published data only (unpublished sought but not used)}</h5>
<ol id="top-references-list-10" class="references-list">
<li>
<ol class="references-and-notes-list">
<li
class="skip-numbering"
value="1">
Lund, et al. [Unpublished study] AB8603. US, 1988. Mentioned in: Walker GA, Mac Hannaford JC. A metaanalysis of randomized, doubleblind, placebocontrolled studies of the effect of buflomedil on intermittent claudication. Fundamental and Clinical Pharmacology 1995;9(4):38794.
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PubMed
</a>
</li>
</ol>
</li>
</ol>
</div>
<div class="refs-list">
<h5 class="refs-list-title">Olsson 1986 {published data only (unpublished sought but not used)}</h5>
<ol id="top-references-list-11" class="references-list">
<li>
<ol class="references-and-notes-list">
<li
class="skip-numbering"
value="1">
Olsson. [Unpublished study] Sweden, 1986. Mentioned in: Walker GA, Mac Hannaford JC. A metaanalysis of randomized, doubleblind, placebocontrolled studies of the effect of buflomedil on intermittent claudication. Fundamental and Clinical Pharmacology 1995;9(4):38794.
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PubMed
</a>
</li>
</ol>
</li>
</ol>
</div>
<div class="refs-list">
<h5 class="refs-list-title">Raithel 1985 {published data only (unpublished sought but not used)}</h5>
<ol id="top-references-list-12" class="references-list">
<li>
<ol class="references-and-notes-list">
<li
class="skip-numbering"
value="1">
Raithel, et al. [Unpublished study] BU3P05. Germany, 1985. Mentioned in: Walker GA, Mac Hannaford JC. A metaanalysis of randomized, doubleblind, placebocontrolled studies of the effect of buflomedil on intermittent claudication. Fundamental and Clinical Pharmacology 1995;9(4):38794.
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</li>
</ol>
</li>
</ol>
</div>
<div class="refs-list">
<h5 class="refs-list-title">Zinnagl 1986 {published data only}</h5>
<ol id="top-references-list-13" class="references-list">
<li>
<ol class="references-and-notes-list">
<li
class="skip-numbering"
value="1">
Zinnagl N. A double blind study of the effects of buflomedil in 40 patients with arterial occlusive disease in Stage IIB [Doppelblindstudie über die Wirksamkeit von Buflomedil an 40 Patienten mit arterieller Verschlusskrankheit im Stadium IIB]. International Symposium on Conservative Therapy of Arterial Occlusive Disease. Bonn, May 2325. New York: Georg Thieme Verlag, 1986.
</li>
</ol>
</li>
</ol>
</div>
</div>
<div class="refs-list">
<h4 class="refs-list-title">Additional references</h4>
<div class="refs-list">
<h5 class="refs-list-title">Baitsch 1983</h5>
<ol id="top-references-list-15" class="references-list">
<li>
<ol class="references-and-notes-list">
<li
class="skip-numbering"
value="1">
Baitsch R. [Unpublished study]. BU2DO2. Germany, 1983. Mentioned in: Walker GA, Mac Hannaford JC. A metaanalysis of randomized, doubleblind, placebocontrolled studies of the effect of buflomedil on intermittent claudication. Fundamental and Clinical Pharmacology 1995; Vol. 9, issue 4:38794.
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</li>
</ol>
</li>
</ol>
</div>
<div class="refs-list">
<h5 class="refs-list-title">Bevan 1992</h5>
<ol id="top-references-list-16" class="references-list">
<li>
<ol class="references-and-notes-list">
<li
class="skip-numbering"
value="1">
Bevan EG, Waller PC, Ramsay LE. Pharmacological approaches to the treatment of intermittent claudication. Drugs and Aging 1992;2(2):12536.
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</li>
</ol>
</li>
</ol>
</div>
<div class="refs-list">
<h5 class="refs-list-title">Cameron 1988</h5>
<ol id="top-references-list-17" class="references-list">
<li>
<ol class="references-and-notes-list">
<li
class="skip-numbering"
value="1">
Cameron HA, Waller PC, Ramsay LE. Drug treatment of intermittent claudication: critical analysis of the methods and findings of published clinical trials, 19651985. British Journal of Clinical Pharmacology 1988;26(5):56976.
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</li>
</ol>
</li>
</ol>
</div>
<div class="refs-list">
<h5 class="refs-list-title">Diamantopoulos 1989</h5>
<ol id="top-references-list-18" class="references-list">
<li>
<ol class="references-and-notes-list">
<li
class="skip-numbering"
value="1">
Diamantopoulos EJ, Raptis SA, ChristodoulouPeters M, Moulopoulos SD. Controlled trial of buflomedil in diabetic peripheral occlusive disease. Ischaemic diseases and the microcirculation. New results. International Symposium. Frankfurt, January 1989:804.
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<div class="refs-list">
<h5 class="refs-list-title">Dickersin 1994</h5>
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Dickersin K, Scherer R, Lefebvre C. Identifying relevant studies for systematic reviews. BMJ 1994;309(6964):128691.
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</li>
</ol>
</li>
</ol>
</div>
<div class="refs-list">
<h5 class="refs-list-title">Fontaine 1954</h5>
<ol id="top-references-list-20" class="references-list">
<li>
<ol class="references-and-notes-list">
<li
class="skip-numbering"
value="1">
Fontaine VR, Kim M, Kieny R. Surgical treatment for peripheral vascular disease [Die chirurgische Behandlung der peripheren Durchblutungsstorungen]. Helvetica Chirurgica Acta 1954;5/6:499533.
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</li>
</ol>
</div>
<div class="refs-list">
<h5 class="refs-list-title">Gardner 1989a</h5>
<ol id="top-references-list-21" class="references-list">
<li>
<ol class="references-and-notes-list">
<li
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Gardner MJ, Altman DG. Estimating with confidence. In: Gardner MJ, Altman DG editor(s). Statistics with confidence: confidence intervals and statistical guidelines. London: BMJ Publishing Group, 1989:35.
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<div class="refs-list">
<h5 class="refs-list-title">Gardner 1989b</h5>
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<ol class="references-and-notes-list">
<li
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Gardner MJ, Altman DG. Estimation rather than hypothesis testing: confidence intervals rather than P values. In: Gardner MJ, Altman DG editor(s). Statistics with confidence: confidence intervals and statistical guidelines. London: BMJ Publishing Group, 1989:619.
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<div class="refs-list">
<h5 class="refs-list-title">Gardner 1989c</h5>
<ol id="top-references-list-23" class="references-list">
<li>
<ol class="references-and-notes-list">
<li
class="skip-numbering"
value="1">
Altman DG, Gardner MJ. Calculating confidence intervals for means and their differences. In: Gardner MJ, Altman DG editor(s). Statistics with confidence: confidence intervals and statistical guidelines. London: BMJ Publishing Group, 1989:207.
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<div class="refs-list">
<h5 class="refs-list-title">Gardner 1989d</h5>
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Gardner MJ, Altman DG. Tables for calculation of confidence intervals. In: Gardner MJ, Altman DG editor(s). Statistics with confidence: confidence intervals and statistical guidelines. London: BMJ Publishing Group, 1989:11129.
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<h5 class="refs-list-title">Jadad 1996</h5>
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<h5 class="refs-list-title">Jepson 1997</h5>
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<h5 class="refs-list-title">Kleijnen 1998</h5>
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<h5 class="refs-list-title">Liard 1997</h5>
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<li
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value="1">
Wood S. Buflomedil to reduce clinical complications of peripheral artery disease? Maybe, maybe not. <a class="external-link-urlize" href="http://www.theheart.org/article/402581.do" rel="nofollow noopener" target="_blank">www.theheart.org/article/402581.do</a> 11 March 2005, issue accessed 26 April 2007.
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<h5 class="refs-list-title">Wurzinger 1987</h5>
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Wurzinger LJ, SchmidSchonbein H. Effect of buflomedil on epinephrineenhanced platelet aggregation in vitro and ex vivo. ArzneimittelForschung 1987;37(10):11135.
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<h4 class="refs-list-title">References to other published versions of this review</h4>
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<h5 class="refs-list-title">De Backer 2000</h5>
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Backer TLM, Vander Stichele RH, Bogaert MG. Buflomedil for intermittent claudication. Cochrane Database of Systematic Reviews 2000, Issue 2. [DOI: 10.1002/14651858.CD000988]
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<h5 class="refs-list-title">De Backer 2007</h5>
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<li>
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<li
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value="1">
De Backer TLM, Bogaert MG, Vander Stichele RH. Buflomedil for intermittent claudication. Cochrane Database of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/14651858.CD000988.pub2]
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<h5 class="refs-list-title">de Backer 2008</h5>
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<li
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value="1">
Backer TLM, Bogaert M, Vander Stichele R. Buflomedil for intermittent claudication. Cochrane Database of Systematic Reviews 2008, Issue 1. [DOI: 10.1002/14651858.CD000988.pub3]
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