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  

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

作　　者：杨莉萍[1] 谢婧[1,2] 刘瑶[1] 胡欣[1] 

机构地区：[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

出　　处：《中国循证医学杂志》2012年第9期1063-1070,共8页Chinese Journal of Evidence-based Medicine

基　　金：中国老年人综合评估和医疗服务体系建立及推广(编号:201002011)

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、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。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, The 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 software RevMan 5.1. Results A total of 13 articles including 14 trials （n=36 855） were included. The results of meta-analysis showed that： a） there was no significant difference 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 significantly 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 significant differences between CYP2C19＊2,＊3 carriers and CYP2C19＊I 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 differences in cardiovascular and bleeding events between the two carriers. Therefore, 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.

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 

分 类 号：R96[医药卫生—药理学]