Plavix clopidogrel: Post-marketing study data

Researchers from McMaster University and colleagues reported data from a genotype analysis of patients with ACS or AF showing that Plavix reduced the rate of cardiovascular events vs. placebo, irrespective of cytochrome P450 2C19 (CYP2C19) loss-of-function carrier status. Specifically, analysis of 5,059 ACS patients from the Phase III CURE trial showed that Plavix significantly reduced the composite rate of cardiovascular death, non-fatal MI or stroke vs. placebo (9.1% vs. 12.6%, p<0.001). The effect of Plavix compared to placebo in reducing the rate of the composite endpoint was similar between carriers of loss-of-function CYP2C19 alleles (8% vs. 11.6%; HR=0.69, 95% CI: 0.49, 0.98) and non-carriers (9.5% vs. 13%; HR=0.72, 95% CI: 0.59, 0.87). In contrast, gain-of-function CYP2C19 allele carriers had a more pronounced reduction in cardiovascular events vs. placebo (7.7% vs. 13%; HR=0.55, 95% CI: 0.42, 0.73) than did non-carriers (10% vs. 12.2%; HR=0.85, 95% CI: 0.68, 1.05).

The researchers noted that 1 possible explanation for their findings, which are in contrast to findings from previous studies, is the difference in the rates of percutaneous coronary intervention (PCI) with stenting. In the CURE trial, only 14.5% of patients underwent PCI with placement of a stent vs. >70% in previous studies. The researchers also asserted that previous studies did not include a randomized control group and thus were unable to exclude potential pleiotropic effects of loss-of-function CYP2C19 alleles. ...