The controversy over the use of genetic testing to guide antiplatelet therapy reminds us of a WWF (Worldwide Wrestling Federation) tag team match.  What we agree upon (the match rules): Clopidogrel is a prodrug activated by several enzymes, including CYP2C19, and common genetic variations alter CYP2C19 activity. Here’s where the wrestling match begins: Are the CYP2C19 genetic…

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The phenomenon of clopidogrel resistance has been much discussed, but no consensus has emerged about the best, or any, response to the problem. Now a review published in JAMA finds no clinically relevant relationship between the CYP2C19 genotype  and cardiovascular events. Michael Holmes and colleagues performed a meta-analysis of 32 studies involving CYP 2C19 genotyping and more…

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French researchers have identified several genetic and clinical factors independently tied to early stent thrombosis. Writing in the Journal of the American Medical Association, Guillaume Cayla and colleagues report on their case-control study comparing 123 patients with definite early stent thrombosis with 246 matched controls without stent thrombosis. The researchers found three genes with variants…

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There has been widespread debate and disagreement over the clinical significance of people with reduced function CYP2C19 genotypes who take clopidogrel. In an effort to shed light on the topic, Jessica Mega and colleagues analyzed data from 9685 patients enrolled in nine clinical trials. Some 26% of patients had 1 reduced-function allele, and 2% had…

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Genetic substudies across a broad range of large clinical trials that used clopidogrel raise questions about the clinical utility of clopidogrel genotyping. The substudies come from large and important trials like PLATO, TRITON-TIMI 38, CURE, and ACTIVE A. A genetic substudy of PLATO finds that ticagrelor is superior to clopidogrel irrespective of genetic subtype. Therefore,…

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