氯吡格雷临床疗效相关性的系统评价

  本文关键词：CYP2C19*2、*3基因多态性与氯吡格雷临床疗效相关性的系统评价，由笔耕文化传播整理发布。

中国循证医学杂志 2012, 12(9): 1063～1070

论 著

二次研究

CYP2C19*2、*3基因多态性与氯吡格雷临床疗效相关性的系统评价△

杨莉萍1 谢 婧1,2 刘 瑶1 胡 欣1*

1. 卫生部北京医院药学部（北京 100730）；2. 沈阳药科大学药学院（沈阳 110016）

摘要 目的 系统评价心血管疾病患者中植入支架后服用氯吡格雷抗血小板作用效果受CYP2C19*2、*3基因多态性的影响程度，以期为其安全使用提供证据。方法 计算机检索EMbase、PubMed、Th e Cochrane Library、Clinical Trial、CBM以及CNKI数据库，查找有关心血管疾病患者携带CYP2C19*2、*3基因与氯吡格雷疗效关系的观察性研究和临床试验，检索时限均从建库截至2011年11月。对符合条件的研究，由2位研究者按照纳入和排除标准，独立筛选文献、提取资料、评价质量，并交叉核对后，采用RevMan 5.1软件进行Meta 分析。结果 共纳入13篇文献，包含14个研究（n=36 855）。Meta分析结果显示：植入支架后服用氯吡格雷，，CYP2C19*2、*3和CYP2C19*1基因携带者的心血管事件及出血事件发生率差异均无统计学意义，但CYP2C19*2、*3基因携带者植入支架后发生血栓的危险较CYP2C19*1基因携带者明显增加（P<0.000 1），其在1个月内发生支架植入后血栓的相对危险度较CYP2C19*1基因携带者增加了92%（P<0.000 1）。结论 在植入支架后使用氯吡格雷的心血管疾病患者中，CYP2C19*2、*3基因携带者比CYP2C19*1基因携带者更易发生支架后血栓，但心血管事件和出血事件发生率相当。鉴于CYP2C19*2、*3基因携带者在植入支架后1个月内形成血栓的风险更大，因此，对拟行PCI手术并用氯吡格雷的患者，我们建议先测CYP2C19基因型，再考虑是否应用氯吡格雷抗血小板预防血栓。

关键词 氯吡格雷；心血管疾病；CYP2C19；基因多态性；Meta分析；安全用药

Correlation between the Genetic Polymorphism of CYP2C19*2, *3 and the Clinical Efficacy of Clopidogrel: A Systematic Review△

YANG Li-ping1, XIE Jing1,2, LIU Yao1, HU Xin1*

1. Department of Pharmacy, Beijing Hospital, Ministry of Public Health, Beijing 100730, China; 2. College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China

Abstract Objective To systematically evaluate anti-platelet effect of clopidogrel influenced by CYP2C19*2,*3 polymorphism in patients with cardiovascular diseases, in order to provide references for its safe medication. Meth-ods Literature was retrieved in electronic databases covering EMbase, PubMed, Th e Cochrane Library, CBM and CNKI from establishment dates to November, 2011. Observational studies and clinical trials were included, cross-checked, as-sessed and pooled for meta-analysis. meta-analysis was performed using the soft ware RevMan 5.1. Results A total of 13 articles including 14 trials (n=36 855) were included. Th e results of meta-analysis showed that: a) there was no signifi cant diff erence in the incidences of cardiovascular events between CYP2C19*2,*3 carriers and CYP2C19*1 carriers; b) the risk of stent thrombosis in CYP2C19*2,*3 carriers was signifi cantly higher than that in CYP2C19*1 carriers (P<0.000 1), and the relative risk of CYP2C19*2,*3 carriers increased 92% within one month (P<0.000 1); c) as for bleeding events, there were no signifi cant diff erences between CYP2C19*2,*3 carriers and CYP2C19*1 carriers. Conclusion Compared with CYP2C19*1 carriers, CYP2C19*2,*3 carriers have a higher risk of stent thrombosis in clopidogrel-treated patients, but there are few diff erences in cardiovascular and bleeding events between the two carriers. Th erefore, CYP2C19*2,*3 carri-ers with cardiovascular diseases and ready to receive PCT are suggested to pay more attention to stent thrombosis when using clopidogrel. We propose that patients with cardiovascular diseases and ready to receive PCT should have CYP2C19 tests to determine the use of antiplatelet drug (clopidogrel) to avoid thrombus.

Key words Clopidogrel; Cardiovascular disease; CYP2C19; Genetic polymorphisms; Meta-analysis; Safe medication

基金项目：中国老年人综合评估和医疗服务体系建立及推广（编号：201002011）△ 系统评价注册号：ChiCTR-OCS-12001901作者简介：杨莉萍，女（1964年～），博士，主任药师。以临床药学，药物基因组学，药物相互作用，老年合理用药为主要研究方向。Email: yanglp_2000@*通讯作者，Email: huxinbjyy@

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  本文关键词：CYP2C19*2、*3基因多态性与氯吡格雷临床疗效相关性的系统评价，由笔耕文化传播整理发布。