Loss-of-function (LOF) variants of cytochrome P450 2C19 (CYP2C19) have been hypothesized to be associated with lesser degrees of platelet inhibition and increased risk for recurrent ischemic events in patients with coronary artery disease on clopidogrel therapy; however, studies from Western countries have yielded mixed results. We aimed to assess the impact of CYP2C19 LOF variants on clinical outcomes from different ethnic groups. Sixteen prospective cohort studies including 7,035 patients carrying ≥ 1 CYP2C19 LOF allele and 13,750 patients with the wild-type genotype were included in this meta-analysis. Carriers of ≥ 1 CYP2C19 LOF allele were at significantly higher risk for adverse clinical events compared to noncarriers during clopidogrel therapy (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.13 to 1.78). The summary OR showed a significant association between CYP2C19 LOF variants and an increased risk of cardiac death (OR 2.18, 95% CI 1.37 to 3.47), myocardial infarction (OR 1.42, 95% CI 1.12 to 1.81), and stent thrombosis (OR 2.41, 95% CI 1.76 to 3.30). Stratified analysis by ethnicity of study population suggested higher odds of adverse clinical events in the Asian population with LOF variants of CYP2C19 (OR 1.89, 95% CI 1.32 to 2.72) compared to Western populations (OR 1.28, 95% CI 1.00 to 1.64). In conclusion, carrier status for LOF CYP2C19 is associated with an increased risk of adverse clinical events in patients with coronary artery disease on clopidogrel therapy despite differences in clinical significance according to ethnicity.
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