不同细胞色素P450酶代谢通路下氯吡格雷联用他汀类药物用于急性冠脉综合征安全性的Meta分析  

Safety of clopidogrel combined with statins on acute coronary syndrome in patients based on metabolic pathways by different cytochrome P450 enzyme:a Meta analysis

作　　者：李剑钦 盛悦越 周寅敏[1] 史蔚青 杨星辰[1] Li Jianqin;Sheng Yueyue;Zhou Yinmin;Shi Weiqing;Yang Xingchen(Department of Pharmacy, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China)

机构地区：[1]上海中医药大学附属龙华医院药学部,上海200032

出　　处：《临床荟萃》2022年第2期101-105,共5页Clinical Focus

基　　金：龙华医院科研基金课题——替格瑞洛与氯吡格雷对急性冠脉综合征介入治疗应用安全分析(Y1817);上海市科学技术委员会科研计划项目——生脉注射液真实世界临床研究(16DZ1920106)。

摘　　要：目的应用Meta分析的方法评价不同细胞色素P450酶代谢通路下氯吡格雷联用他汀类药物用于急性冠脉综合征(acute coronary syndrome,ACS)的安全性。方法计算机检索万方数据库、中国生物医学文献数据库、中国期刊全文数据库、维普数据库以及英文数据库Science Citation Index(SCI)、Pubmed、Embase数据库,检索年限从建库至2020年4月。对收集的文献进行质量评价,使用STATA 14.0软件对提取的数据进行Meta分析。结果最终入选9篇文献,11008例患者,其中服用经CYP3A4代谢的他汀类药物(包括阿托伐他汀,辛伐他汀)的患者7179例,服用未经CYP3A4代谢的他汀类药物(包括瑞舒伐他汀,氟伐他汀,普伐他汀)的患者3829例。Meta分析显示,在欧美人群中,未经CYP3A4代谢组的他汀类药物联用氯吡格雷的主要心血管不良事件(major adverse cardiac events,MACE)发生情况少于经CYP3A4代谢组,差异具有统计学意义(P<0.05),而在亚洲人群中两者差异无统计学意义(P>0.05);其中,患者死亡,心肌梗死,卒中的发生率两者差异也均无统计学意义(P>0.05)。结论未经CYP3A4代谢组的他汀类药物联用氯吡格雷或能减少欧美人群的MACE发生率,而在亚洲人群中两者差异无统计学意义。Objective To evaluate the safety of clopidogrel in combination with statins for acute coronary syndrome(ACS)under different cytochrome P450 enzyme metabolic pathways by Meta-analysis.Methods A computer retrieval was performed in several databases,as Wanfang Data,Chinese Bio-medicine Database,China National Knowledge Infrastructure,VIP database,Science Citation Index(SCI),Pubmed and Embase.The retrieval period from the library construction to April 2020.After evaluating the quality of these literatures,Meta-analysis was conducted by STATA 14.0 for these data.Results At last,9 eligible papers included 11,008 patients;of which,7,179 patients taking statins metabolized by CYP3A4(Atorvastatin and Simvastatin)and 3,829 patients taking statins not metabolized by CYP3A4(Rosuvastatin,Fluvastatin and Pravastatin).Meta-analysis demonstrated that Major Adverse Cardiac Events(MACE)were less frequent statin combined with clopidogrel in non-CYP3A4 metabolism than in CYP3A4 metabolism in Europe and America,with statistically significant difference between the two groups(P<0.05).However,there was no statistically significant difference between the two groups in Asian populations(P>0.05),of which,no statistically significant difference was also found in death,myocardial infarction and stroke(P>0.05).Conclusion A combination of statins non-CYP3A4 metabolite clopidogrel is capable of reducing the risk for MACE in European and American populations,but not in Asian populations.

关 键 词：急性冠脉综合征 氯吡格雷 他汀 主要心血管不良事件 CYP3A4 META分析 

分 类 号：R541.4[医药卫生—心血管疾病]