This article is more than 5 years old. Information may no longer be current.
Clopidogrel unaffected by CYP2C19 loss-of-function alleles in patients with ACS, AF
Paré G. N Engl J Med. 2010;363:1704-1714.
Click Here to Manage Email Alerts
Data from two large, randomized trials have suggested that the effect of clopidogrel when compared with placebo remained consistent regardless of CYP2C19 loss-of-function allele status for patients with acute coronary syndromes or atrial fibrillation.
“Recent reports suggest that certain common genetic variants, involving the hepatic cytochrome P450 system, that are involved in the conversion of clopidogrel to its active metabolite are associated with an increased rate of recurrent CV events, implying that the benefits of clopidogrel may be attenuated in patients with these genetic variants,” study researcher Guillaume Paré, MD, and colleagues wrote. “Specifically, in patients who are carriers of a loss-of-function CYP2C19 allele (including the *2 and *3 alleles), the conversion of clopidogrel to its active metabolite may be reduced, resulting in decreased inhibition of platelets.”
Researchers tested this hypothesis by examining the efficacy and safety of clopidogrel vs. placebo according to genotype status (CYP2C19*2, *3 or *17) among patients in the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) and Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE A) randomized trials. The study population included patients with ACS (n=5,059) and AF (n=1,156), and the primary efficacy endpoint was defined as the rate of CV events.
Among patients with ACS, researchers reported a significant reduction in CV events in the clopidogrel arm when compared with placebo (9.1% vs. 12.6%; clopidogrel HR=0.71; 95% CI, 0.60-0.84). The effect of clopidogrel vs. placebo was similar in reducing the primary efficacy between carriers of loss-of-function alleles (*2 and *3) and noncarriers (P=.84); however, gain-of-function (*17) carriers derived more benefit from clopidogrel treatment as compared with placebo than noncarriers (P=.02).
In the AF group, a hazard reduction was reported in the primary endpoint for patients with AF given clopidogrel (20% vs. 26.3%; HR=0.74; 95% CI, 0.58-0.94). Researchers reported no evidence of an interaction with either efficacy or bleeding between the study treatment and the metabolizer phenotype, loss-of-function carrier status or gain-of-function carrier status.
“Our study shows that CYP2C19 loss-of-function variants do not modify the efficacy and safety of clopidogrel. Therefore, loss-of-function allele carrier status should not preclude the use of clopidogrel at currently recommended doses in patients with ACS whose condition is being managed conservatively,” Paré and colleagues wrote. “Although similar results were observed in patients with AF, larger studies will be needed to definitively rule out a genetic effect of the loss-of-function alleles in this patient population.”
 |
Follow CardiologyToday.com on Twitter. |