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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EGenetic variations that are related to clopidogrel metabolism did not diminish clopidogrel efficacy in patients with acute coronary syndromes or atrial fibrillation, according to new data from the Clopidogrel in Unstable Angina to Prevent Recurrent Events [CURE] and Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events [ACTIVE] trials.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EMyocardial Infarction\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology Genomics\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EArrhythmias\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EGenetic variations that are related to clopidogrel metabolism did not diminish clopidogrel efficacy in patients with acute coronary syndromes (ACS) or atrial fibrillation (AF), according to new data from two clinical trials. Guillaume Par\u00e9, MD, MSc, McMaster University, Hamilton, Ontario, Canada, presented new findings from the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) and Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE) trials.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe CYP2C19 gene is associated with the conversion of clopidogrel to its active metabolite. Variations in this gene include the loss-of-function CYP2C19 alleles (CYPC19*2 and CYPC19*3), which slow this conversion, and the gain-of-function CYP2C19 allele (CYPC19*17), which facilitates the metabolism of clopidogrel to its active form. To examine the influence of genetic variations on platelet response, Prof. Par\u00e9 and colleagues evaluated safety and efficacy outcomes among patients who were enrolled in the CURE (n=5059) and ACTIVE (n=1156) trials according to CYP2C19 genotype (*2, *3, or *17).\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EIn the CURE trial, there was no interaction between loss-of-function CYP2C19 alleles and the efficacy of clopidogrel relative to placebo (p=0.12). Clopidogrel provided a similar magnitude of protection against the primary endpoint compared with placebo in carriers of a loss-of-function allele (8.0% vs 11.6%; HR, 0.69; 95% CI, 0.49 to 0.98) and in those who did not carry a loss-of-function allele (9.5% vs 13.0%; HR, 0.72; 95% CI, 0.59 to 0.87).\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EBy comparison, patients who were carriers of the CYP2C19 gain-of-function allele derived a greater benefit from clopidogrel than noncarriers (p=0.02) in the CURE trial. Clopidogrel significantly reduced the risk of the primary outcome versus placebo among gain-of-function allele carriers (7.7% vs 13.0%; HR, 0.55; 95% CI, 0.42 to 0.73) but not among noncarriers of the CYP2C19 gain-of-function allele (10.0% vs 12.2%; HR, 0.85; 95% CI, 0.68 to 1.05).\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EIn the ACTIVE A trial, no differences in clopidogrel efficacy were observed between carriers and noncarriers of CYP2C19 loss-of-function alleles (p=0.87) or between carriers and noncarriers of the gain-of-function CYP2C19 allele (p=0.34). In both the CURE and ACTIVE A trials, bleeding risk among clopidogrel-treated patients did not vary according to CYP2C19 genotype.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EIn addition to ACTIVE A, future larger studies will be needed to rule out an adverse effect of CYP2C19 loss-of-function alleles on clopidogrel efficacy in patients with AF. However, the CURE trial provided strong data that support the continued use of clopidogrel in patients with ACS, regardless of CYP219 genotype status. In particular, conservatively managed ACS patients who carry the CYP2C19 loss-of-function allele should not be restricted from using clopidogrel at currently recommended doses, Prof. Par\u00e9 concluded. Further studies will be needed to define the clinical role, if any, of the gain-of-function allele.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2010 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/10\/8\/33.2.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzmpk5\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}