CYP2C19 Genotype May Not Increase Risk of Cardiovascular Events in Patients Taking Clopidogrel

DynaMed Weekly Update - Volume 7, Issue 1

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Clopidogrel (Plavix) comes with a boxed warning, issued by the FDA in 2010, suggesting genetic testing for the CYP2C19 genotype prior to use. The warning was based on data suggesting that slow metabolism of the drug due to the genotype was associated with decreased efficacy and increased risk of cardiovascular events. The American Heart Association and the American College of Cardiologists issued a consensus statement disputing the warning for insufficient evidence to recommend routine screening (J Am Coll Cardiol. 2010 Jul 20;56(4):321). A new systematic review of 32 studies appears to support this dissenting view.

The review included data from 42,016 patients (mean age 63 years) with acute coronary syndrome or stable coronary heart disease. There was a total of 3,545 cardiovascular disease events. In analysis of 26 observational studies, presence of ≥ 1 CYP2C19 allele was associated with increased risk of cardiovascular disease events in patients taking clopidogrel (relative risk 1.18, 95% CI 1.09-1.28). However, these results appear to have been due to data from small studies and in an analysis limited to 4 studies with at least 200 events (10,570 patients), there was no significant difference in event rates between carriers and non-carriers.

In a subgroup meta-analysis of 11,012 patients with the CYP2C19 genotype from 4 randomized trials, clopidogrel was associated with reduced risk of cardiovascular events compared to placebo (risk ratio 0.8, 95% CI 0.72-0.89). This risk reduction was similar to that found in the overall analysis disregarding genotype (risk ratio 0.84, 95% CI 0.79-0.89). The risk of major bleeding was increased with clopidogrel in both subgroup and overall analyses (level 2 [mid-level] evidence)(JAMA 2011 Dec 28;306(24):2704).

For more information, see the Clopidogrel topic in DynaMed.