CHICAGO Although the U.S. Food and Drug Administration (FDA) has recommended that a certain type of genetic testing (for the genotype CYP2C19) be considered before prescribing the drug clopidogrel to identify individuals who may be less responsive to the medication, a review and analysis of previous studies did not find an overall significant association between the CYP2C19 genotype and cardiovascular events, according to a study in the December 28 issue of JAMA.
Clopidogrel is an antiplatelet drug used by approximately 40 million patients worldwide to treat or prevent atherothrombotic (blood clot from thickening of inner lining of arteries) events and after percutaneous coronary revascularization (such as balloon angioplasty). "Despite the overall benefit, some individuals may be less responsive to clopidogrel than others because clopidogrel is a prodrug activated by several enzymes, including CYP2C19, and common genetic variation in CYP2C19 alters enzyme activity," according to background information in the article. The American Heart Association and American College of Cardiologists have argued evidence is insufficient to support CYP2C19 genotype testing.
Michael V. Holmes, M.B.B.S., M.Sc., of University College London, and colleagues conducted a systematic review and meta-analysis to assess the strength and quality of evidence on the association of CYP2C19 genotype with responsiveness to clopidogrel. The researchers conducted a search of the medical literature and identified 32 studies that met criteria for inclusion. These included studies that reported clopidogrel metabolism, platelet reactivity or clinically relevant outcomes (cardiovascular disease [CVD] events and bleeding), and information on CYP2C19 genotype.
The 32 studies included 42,016 patients reporting 3,545 CVD events, 579 stent thromboses, and 1,413 bleeding events. Six studies were randomized trials ("effect-modification" design) and the remaining 26 repo
|Contact: Michael V. Holmes, M.B.B.S., M.Sc.|
JAMA and Archives Journals