Abstract 13944: Cardiovascular Outcomes in Drug Eluting Stent Patients on Clopidogrel Based Genetic Variants in CYPC219*2, CYP2C19*17, and ABCB1
Background: Clopidogrel requires the P-450 enzyme CYP2C19 for activation. Failure of anti-platelet therapy with clopidogrel has been associated with a loss of function variant in the CYP2C19 gene (CYP2C19*2). Clopidogrel efficacy may also be affected by the p-glycoprotein (coded by ABCB1). Here we tested the hypothesis that reduced function variants in the CYP2C19 and ABCB1 genes and a CYP2C19 gain-of-function variant (CYP2C19*17) interact to modify risk for major adverse cardiovascular events within 1 year for recipients of drug-eluting stents (DES).
Methods: We studied patients enrolled in the Intermountain Heart Collaborative Study who were prescribed clopidogrel after DES placement (n=1034). Genotyping was done by Taqman real-time PCR for the three variants (CYP2C19*2 and *17 and ABCB1 3435C>T). Endpoints were myocardial infarction (MI) and MI/death assessed at 1 year following stenting. Cox Regression was used, controlling for age and sex.
Results: CYP2C19*2 was significantly associated with both 1-yr MI (p=0.02; HR=1.75; 95% CI 1.09, 2.81) and 1-yr MI/death (p=0.04; HR=1.54; 95% CI 1.02, 2.32) when only CYP2C19*2 was in the model. Testing CYP2C19*17 in the model, while not significant when tested alone and not significantly increasing model predictive ability when added to CYP2C19*2 (incremental p=0.21), did slightly decrease the significance of CYP2C19*2 for both 1-yr MI (p=0.06; HR=1.61; 95% CI 0.99, 2.63) and 1-yr MI/death (p=0.10; HR=1.43; 95% CI 0.93, 2.19). ABCB1 3435 was not associated with either outcome and did not change model prediction.
Conclusions: CYP2C19*2 genotype alone optimally predicts MI and MI/death after DES. Although its predictive ability is modestly offset by CYP2C19*17, the addition of this variant does not improve model predictive ability. By themselves, neither CYP2C19*17 nor ABCB1 3435 are significantly associated with MI or MI/death in patients with DES on clopidogrel.
- © 2011 by American Heart Association, Inc.