Plavix clopidogrel: Postmarketing study data

Researchers at University College London and colleagues reported data from a meta-analysis showing no significant association between cytochrome P450 2C19 (CYP2C19) genotype and cardiovascular events in patients receiving Plavix, although there was an association between the genotype and responsiveness to the drug. The results appear to contradict a 2010 black box warning added to Plavix's label about diminished effectiveness in patients with a genetic variation in CYP2C19 that reduces functioning of the CYP2C19 liver enzyme. The warning says that patients with the variant exhibit higher cardiovascular event rates following ACS or percutaneous coronary intervention (PCI) than patients with normal CYP2C19 function (see BioCentury, March 15, 2010).

Specifically, an analysis of 6 randomized trials of Plavix showed that the CYP2C19 genotype had no significant effect on cardiovascular events or bleeding (p>0.05 for both). In 26 trials in which all patients received Plavix, patients with >=1 CYP2C19 allele associated with lower enzyme activity had lower levels of active clopidogrel metabolites, less platelet inhibition, a lower risk of bleeding and an increased risk of cardiovascular events. However, the researchers also found evidence of small-study bias and when only studies with >=200 events were included the association between the genotype and responsiveness to Plavix was reduced. ...