Choi Ik Jun, Koh Yoon-Seok, Park Mahn-Won, Her Sung Ho, Choi Yun-Seok, Park Chul-Soo, Park Hun-Jun, Kim Pum-Joon, Chung Wook-Sung, Kim Ho-Sook, Shin Jae-Gook, Seung Ki-Bae, Chang Kiyuk
aDivision of Cardiology, Department of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul bIncheon St. Mary's Hospital cSeoul St. Mary's Hospital, Incheon dDaejeon St. Mary's Hospital, Daejeon eYeouido St. Mary's Hospital, Seoul fDepartment of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Republic of Korea.
Medicine (Baltimore). 2016 Jun;95(26):e4049. doi: 10.1097/MD.0000000000004049.
CYP2C19 loss-of-function (LOF) alleles adversely affect clinical outcome of clopidogrel therapy. Recent introduction of a newer-generation drug-eluting stent (DES) has significantly reduced the occurrence of stent thrombosis.The aim of this study was to evaluate the impact of CYP2C19 LOF alleles on clinical outcome in patients treated with the newer-generation DES.The effects of CYP2C19 genotypes were evaluated on clinical outcome of clopidogrel therapy in 2062 patients treated with percutaneous coronary intervention using either first-generation DES (sirolimus- and paclitaxel-eluting stent, n = 1349) or newer-generation DES (everolimus- and zotarolimus-eluting stent, n = 713). The primary clinical outcome was major cardiac and cerebrovascular event (MACCE) including cardiac death, nonfatal myocardial infarction, stroke, and stent thrombosis during 1 year of follow-up.CYP2C19 LOF alleles were significantly associated with a higher risk of MACCE in patients treated with first-generation DES (hazard ratio [HR] 2.599, 95% confidence interval [CI] 1.047-6.453; P = 0.034). In contrast, CYP2C19 LOF alleles were not associated with primary outcome in newer-generation DES (HR 0.716, 95% CI 0.316-1.622; P = 0.522). In the further multivariate analysis, CYP2C19 LOF alleles were not associated with MACCE in patients receiving newer-generation DES (adjusted HR 0.540, 95% CI 0.226-1.291; P = 0.166), whereas they were demonstrated to be an independent risk factor for MACCE in those implanted with first-generation DES (adjusted HR 3.501, 95% CI 1.194-10.262; P = 0.022).In contradiction to their clinical impact in first-generation DES era, CYP2C19 LOF alleles may not affect clinical outcome of clopidogrel therapy in patients treated with newer-generation DES.
细胞色素P450 2C19功能缺失（LOF）等位基因对氯吡格雷治疗的临床结局有不利影响。新一代药物洗脱支架（DES）的近期应用显著降低了支架血栓形成的发生率。本研究的目的是评估CYP2C19 LOF等位基因对接受新一代DES治疗患者临床结局的影响。在2062例接受经皮冠状动脉介入治疗的患者中，评估了CYP2C19基因型对氯吡格雷治疗临床结局的影响，这些患者使用的是第一代DES（西罗莫司和紫杉醇洗脱支架，n = 1349）或新一代DES（依维莫司和佐他莫司洗脱支架，n = 713）。主要临床结局是主要心脑血管事件（MACCE），包括随访1年内的心源性死亡、非致死性心肌梗死、中风和支架血栓形成。CYP2C19 LOF等位基因与接受第一代DES治疗患者发生MACCE的较高风险显著相关（风险比[HR] 2.599，95%置信区间[CI] 1.047 - 6.453；P = 0.034）。相比之下，CYP2C19 LOF等位基因与新一代DES治疗的主要结局无关（HR 0.716，95% CI 0.316 - 1.622；P = 0.522）。在进一步的多变量分析中，CYP2C19 LOF等位基因与接受新一代DES治疗患者的MACCE无关（校正HR 0.540，95% CI 0.226 - 1.291；P = 0.166），而在植入第一代DES的患者中，它们被证明是MACCE的独立危险因素（校正HR 3.501，95% CI 1.194 - 10.262；P = 0.022）。与它们在第一代DES时代的临床影响相反，CYP2C19 LOF等位基因可能不会影响接受新一代DES治疗患者氯吡格雷治疗的临床结局。
