Abstract 16546: Difference in Impact of CYP2C19 Polymorphism on Platelet Reactivity and Clinical Outcomes Between Acute Coronary Syndrome (ACS) and Stable Angina
Background: As compared with Caucasian, Japanese more often carry the CYP2C19 loss-of-function (LOF) allele with the CYP2C19*3 variant. The difference in influence of the CYP2C19 LOF alleles (*2 and *3) on clopidogrel response and clinical outcomes between ACS and stable angina (SA) has not been reported. The Aim was to examine the difference in impact of the CYP2C19 variants on platelet reactivity and prognosis between ACS and SA after stent implantation.
Methods: We enrolled 509 patients following stent implantation, taking dual antiplatelet therapy with 100 mg/day aspirin and 75 mg/day clopidogrel as a maintenance dose after a loading dose of clopidogrel 300 mg, in this prospective study with 12 months follow-up. Patients were divided into ACS (n=217, male 71%, age 69.9 ys) and SA (n=292, male 70%, age 70.3 ys). Adenosine diphosphate induced platelet aggregation using light transmission aggregometer was measured as response to clopidogrel. CYP2C19 polymorphism was examined, and classified into three phenotypes: (1) extensive metabolizer (EM) carrying normal function (wild-type) alleles (CYP2C19*1/*1), (2) intermediate metabolizer (IM) carrying one LOF allele (*1/*2, *1/*3), and (3) poor metabolizer (PM) carrying two LOF alleles (*2/*2, *2/*3, *3/*3). Clinical endpoint was cardiovascular death, ACS, stroke, any urgent revascularization, and intraprocedural thrombotic events.
Results: There was an increased platelet reactivity in ACS group compared with SA (4588AU*min vs 4125, P=0.09). ACS showed higher ratio of adverse clinical events compared with SA (15.7 vs 6.8%, P<0.05). There was no difference in distribution of EM, IM, and PM between ACS and SA (ACS vs SA, EM; 33% vs 33, IM; 44 vs 46, PM; 18 vs 19%), however, the ratio of PM is very higher in Japanese than Caucasian. In ACS, the incidence of adverse clinical events was significantly higher in PM than EM (24.2 vs 7.2%, P<0.05), however, there were no differences in cardiovascular event rate among EM, IM, and PM in SA. Intraprocedural thrombotic events were frequently seen in PM of ACS group compared with other genotypes of ACS or SA.
Conclusions: In patients with stent implantation, impact of CYP2C19 LOF polymorphism on clinical outcomes is more powerful in ACS compared with SA patients.
- © 2013 by American Heart Association, Inc.