Clopidogrel is the mainstay for antiplatelet treatment after percutaneous coronary intervention (PCI). The relationship of platelet reactivity and genetic polymorphism with clinical outcomes with newer-generation drug-eluting stents is unclear. We analysed 4,587 patients for the most powerful single-nucleotide polymorphisms (CYP2C19, CYP2C9, ABCB1, PON1, and P2Y12) related to on-treatment platelet reactivity (OPR). The optimal cut-off value of high OPR for major adverse thrombotic events was 266. CYP2C19 was significantly associated with high OPR and the number of CYP2C19∗R (∗2 or∗3) alleles was proportional to the increased risk of high OPR. Death, myocardial infarction (MI), stroke, stent thrombosis, and bleeding events were assessed during a 1-year follow-up period. Primary endpoints were death and non-fatal MI. The cumulative 1-year incidence of death and stent thrombosis was significantly higher in patients with CYP2C19∗2/∗2, CYP2C19∗2/∗3, and CYP2C19∗3/∗3 (Group 3) than in patients with CYP2C19∗1/∗1 (Group 1). Multivariate Cox proportional hazard model showed that cardiac death risk was significantly higher in Group 3 than in Group 1 (hazard ratio 2.69, 95% confidence interval 1.154-6.263, p = 0.022). No association was reported between bleeding and OPR. Thus, CYP2C19 may exert a significant impact on the prognosis of PCI patients even in the era of newer-generation drug-eluting stents.
Bibliographical noteFunding Information:
The GENIUS study was funded by Dong-A ST CO., LTD. We declare that the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We deeply appreciate all other investigators of GENIUS study (YoungKeun Ahn, YoungWon Yoon, Myoung-Ho Yoon, DongHun Yang, Jae-Bin Seo, SeungMin Choi, and JongSeon Park). Finally, we are indebted to all clinical research assistants of the involved institutes, especially Yun Gyeong Oh. We also thank Dr. Cheol Woong Yu for his critical revision of the study interpretation and manuscript.
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