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[Relevance of CYP2C19*2 regarding platelet reactivity in patients with acute coronary syndrome treated with clopidogrel.]


Med Clin (Barc). 2013 Jul 10;


Authors: Cano P, Consuegra-Sánchez L, Conesa P, Torres-Moreno D, Jaulent L, Dau D, Picó F, Villegas M


Abstract

BACKGROUND AND OBJECTIVE: Previous studies have shown that the metabolism of P2Y12 receptor blockers is influenced not only by CYP2C19*2 but also by PON1-Q192R alelles. We aimed to evaluate the impact of CYP2C19*2 and PON1-Q192R polymorphisms carriage in platelet reactivity and clinical outcome in patients with ischemic heart disease undergoing cardiac catheterization.

PATIENTS AND METHOD: We recruited prospectively patients with acute coronary syndrome undergoing cardiac catheterization (n=247). We evaluated the genotype (CYP2C19*2, CYP2C19*17, PON1-Q192R) with TaqMan(®) assay and platelet aggregometry in all patients. We assessed both in and out-of-hospital events (unstable angina, periprocedural and spontaneous myocardial infarction, myocardial infarction, all-cause death, stent thrombosis and stroke) during follow-up.

RESULTS: Carriers of CYP2C19*2 alleles showed a significant higher residual platelet reactivity (PRU, mean [SD], 252 [76] vs. 287 [74], P=.002). Carriers of PON1-Q192R CT(RQ) and TT(QQ) alleles and CYP2C19*17 did not present a different response to clopidogrel. In a multivariable setting for the prediction of platelet reactivity, the contribution of CYP2C19*2 was modest (Wald=7.5; odds ratio [OR] for≥1 alelle *2=2,786, 95% confidence interval [95% CI] 1,337-5,808). Independent predictors were baseline hemoglobin levels (g/dL, OR .666, 95% CI .555-.801) and the use of statins (OR .376, 95% CI .162-.873). Body mass index was a risk factor (OR 1,074, CI 95% 1,005-1,148). Studied polymorphisms did not predict an adverse outcome.

CONCLUSIONS: CYP2C19*2 polymorphism influenced moderately platelet reactivity but did not show an impact on clinical outcome in patients with acute coronary syndrome. Neither CYP2C19*17 nor PON1-Q192R polymorphisms showed an impact upon platelet reactivity or outcome.

PMID: 23850044 [PubMed - as supplied by publisher]