Effects of CYP2C19 allelic variants on inhibition of platelet aggregation and major adverse cardiovascular events in Japanese patients with acute coronary syndrome: The PRASFIT-ACS study
Effects of CYP2C19 allelic variants on inhibition of platelet aggregation and major adverse cardiovascular events in Japanese patients with acute coronary syndrome: The PRASFIT-ACS study
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DOI：
10.1016/j.jjcc.2015.07.019
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发表时间：
2016-07-01
影响因子：
2.5
通讯作者：
Saito, Shigeru
中科院分区：
文献类型：
--
作者：
Ogawa, Hisao;Isshiki, Takaaki;Saito, Shigeru
背景：我们研究了细胞色素P450 2C19 （CYP2C19）多态性对普拉格雷和氯吡格雷在日本急性冠脉综合征（ACS）患者经皮冠状动脉介入治疗（PCI） （prasfitt -ACS）研究中的疗效和安全性的影响。方法：接受PCI治疗的日本ACS患者随机（双盲）接受普拉格雷（负荷/维持剂量：20/3.75 mg）或氯吡格雷（300/75 mg）加阿司匹林治疗24-48周。对773/1363例患者进行药物基因组学分析。P2Y（12）反应单位（PRU）采用VerifyNow (R) P2Y（12）测定法（Accumetrics, San Diego， CA， USA）测定。CYP2C19基因型分为广泛代谢型（EM）、中间代谢型（IM）和差代谢型（PM）。结果：总体而言，普拉格雷组有39.2%和60.8%的患者被归类为EM，氯吡格雷组有35.2%和64.8%的患者被归类为IM + PM。在EM患者中，在负荷剂量后2-4和5-12小时，普拉格雷组的PRU显著低于氯吡格雷组，但从第4周开始，两组的PRU相似。在IM + PM患者中，在整个研究过程中，普拉格雷组的PRU明显低于氯吡格雷组。在EM患者中，24周时普拉格雷组的主要不良心血管事件（MACE）发生率为11.8%，氯吡格雷组为11.9%[风险比（HR）： 0.99, 95%可信区间（CI）： 0.50-1.96]。在IM + PM患者中，普拉格雷组MACE发生率为9.3%，氯吡格雷组MACE发生率为12.5% （HR: 0.78, 95% CI: 0.45-1.35）。两组各基因型的大出血、小出血和临床相关出血的发生率相似。结论：无论CYP2C19表型如何，普拉格雷在日本ACS患者中表现出比氯吡格雷更一致的抗血小板作用。(C) 2015日本心脏病学院。Elsevier Ltd.出版。版权所有。
Background: We examined the effects of cytochrome P450 2C19 (CYP2C19) polymorphisms on the efficacy and safety of prasugrel and clopidogrel in a post hoc analysis of the PRASugrel compared with clopidogrel For Japanese patIenTs with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) (PRASFIT-ACS) study.Methods: Japanese ACS patients undergoing PCI were randomized (double-blind) to receive prasugrel (loading/maintenance dose: 20/3.75 mg) or clopidogrel (300/75 mg) plus aspirin for 24-48 weeks. Pharmacogenomic analyses were conducted in 773/1363 patients. P2Y(12) reaction units (PRU) were determined using the VerifyNow (R) P2Y(12) assay (Accumetrics, San Diego, CA, USA). CYP2C19 genotypes were classified as extensive metabolizers (EM), intermediate metabolizers (IM), and poor metabolizers (PM).Results: Overall, 39.2% and 60.8% of patients in the prasugrel group and 35.2% and 64.8% of patients in the clopidogrel group were classified as EM and IM + PM, respectively. Among EM patients, PRU was significantly lower in the prasugrel group than in the clopidogrel group at 2-4 and 5-12 h after the loading dose, but was similar in both groups from week 4 onwards. Among IM + PM patients, PRU was significantly lower in the prasugrel group than in the clopidogrel group throughout the study. Among EM patients, the incidence of major adverse cardiovascular events (MACE) at 24 weeks was 11.8% in the prasugrel group and 11.9% in the clopidogrel group [hazard ratio (HR): 0.99, 95% confidence interval (CI): 0.50-1.96]. Among IM + PM patients, the incidence of MACE was 9.3% in the prasugrel group and 12.5% in the clopidogrel group (HR: 0.78, 95% CI: 0.45-1.35). The incidences of major, minor, and clinically relevant bleeding were similar between the two groups for each genotype.Conclusions: Prasugrel showed more consistent antiplatelet effects than clopidogrel in Japanese ACS patients irrespective of the CYP2C19 phenotype. (C) 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.