P4010The effect of CYP2C19 gene polymorphism on clinical outcomes in patients with CAD receiving antiplatelet therapy

Abstract

Background: The effect of CYP2C19 gene polymorphism on clinical outcomes of patients with coronary artery disease (CAD) treated with clopidogrel is controversial. More than ten previous meta-analyses yield discordant conclusions. And there are some new studies about this issue in recent years. Objective: To evaluate the effect of CYP2C19 gene polymorphism on clinical outcomes in patients with CAD receiving antiplatelet therapy. Method: We conducted a comprehensive search in PubMed and EMBASE from their inceptions to January 20,2017. Studies that reported clopidogrel loading dose, clinically relevant outcomes (adverse cardiovascular events, stent thrombosis and bleeding) and information on CYP2C19 genetype were included. The primary efficacy endpoint was major adverse cardiovascular events (MACE), defined as a composite of CV death, nonfatal myocardial infarction, stroke, unstable angina coronary revascularization and stent thrombosis (ST). The safety endpoint was any kind of bleeding. Results:We retrieved 34 studies of 32746 patients reporting 3157 cardiovascular events, 378 stent thrombosis and 898 bleeding. The primary analysis about cardiovascular events was resricted to studies with more than 200 participants, which included 25 studies and a total of 30441 participants. At least one CYP2C19 loss-of-function alleles (∗2 and/or ∗3) carriers were at increased risk of MACE campared with non-carriers (10.3% vs. 8.7%; risk ratio (RR): 1.51, 95% confidence interval (CI): 1.28-1.77, p<0.00001) (Figure 1). The association was more significant between two loss-of-function (LOF) alleles carriers and risk of MACE was more significant (RR: 2.14, 95% CI: 1.67-2.75, p<0.00001) (Figure 2). ST was also more frequent in carriers of LOF alleles (RR: 2,28, 95% CI: 1.81-2.88) (Figure 3). In additon, LOF alleles carriers did not present a lower risk of bleeding (RR: 0.91; 95% CI: 0.77-1.06) (Figure 4). Conclusion: Carriers of CYP2C19 loss-of-function alleles are at higher risk of adverse cardiovascular events and stent thrombosis compared with non-carriers among patients with coronary artery disease treated with clopidogrel. (Figure Presented).