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

doi:10.3969/j.issn.1004-583X.2022.02.001

摘要/Abstract

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,11 008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7 179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3 829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。

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

Abstract:

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.

Key words: acute coronary syndrome, clopidogrel, statin, major adverse cardiac events, CYP3A4, Meta-analysis

中图分类号:

R541.4

李剑钦, 盛悦越, 周寅敏, 史蔚青, 杨星辰. 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[J]. 临床荟萃, 2022, 37(2): 101-105.

Li Jianqin, Sheng Yueyue, Zhou Yinmin, Shi Weiqing, Yang Xingchen. Safety of clopidogrel combined with statins on acute coronary syndrome in patients based on metabolic pathways by different cytochrome P450 enzyme: a Meta analysis[J]. Clinical Focus, 2022, 37(2): 101-105.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2022.02.001

https://huicui.hebmu.edu.cn/CN/Y2022/V37/I2/101

图/表 4

参考文献 17

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作者	年份	地区	样本量	Clo [LD/MD(mg)]	干预措施	随访时间	终点事件	Jadad 评分
Zhang^[9]	2015	中国	51	300/75	G1:Clo+A20 mg G2:Clo+R10 mg	6 months	MACE	5
Lotfi^[10]	2008	美国	3 038	-/-	G1:Clo+A80 mg G2:Clo+P40 mg	2 years	MACE, 死亡, MI, 卒中, UA	4
Suh^[11]	2014	韩国	556	300~600/75	G1:Clo+A20 mg G2:Clo+R10 mg	6 months	MACE, 死亡, MI, 卒中, TLR, ST	4
Saw^[12]	2007	美国	4 997	-/75	G1:Clo+A/S/L G2:Clo+P/F	28 months	MACE	6
Lablanche^[13]	2010	法国	829	-/-	G1:Clo+A80 mg G2:Clo+R20 mg	3 months	MACE, 死亡, MI, 卒中	7
韩雅玲^[14]	2009	中国	1 275	300/75	G1:Clo+A20 mg G2:Clo+P20 mg	1 year	MACE, 死亡, MI, 卒中, TVR, Bleeding	4
赵嫣^[15]	2008	中国	60	300/75	G1:Clo+A10 mg G2:Clo+F40 mg	6 months	MACE, 死亡	4
王倩^[16]	2010	中国	100	300/75	G1:Clo+S20 mg G2:Clo+F40 mg	1 month	MACE	4
刘新兵^[17]	2007	中国	102	300/75	G1:Clo+A10-20 mg G2:Clo+P20-40 mg	2 weeks	死亡, MI	4

作者	年份	地区	样本量	Clo [LD/MD(mg)]	干预措施	随访时间	终点事件	Jadad 评分
Zhang^[9]	2015	中国	51	300/75	G1:Clo+A20 mg G2:Clo+R10 mg	6 months	MACE	5
Lotfi^[10]	2008	美国	3 038	-/-	G1:Clo+A80 mg G2:Clo+P40 mg	2 years	MACE, 死亡, MI, 卒中, UA	4
Suh^[11]	2014	韩国	556	300~600/75	G1:Clo+A20 mg G2:Clo+R10 mg	6 months	MACE, 死亡, MI, 卒中, TLR, ST	4
Saw^[12]	2007	美国	4 997	-/75	G1:Clo+A/S/L G2:Clo+P/F	28 months	MACE	6
Lablanche^[13]	2010	法国	829	-/-	G1:Clo+A80 mg G2:Clo+R20 mg	3 months	MACE, 死亡, MI, 卒中	7
韩雅玲^[14]	2009	中国	1 275	300/75	G1:Clo+A20 mg G2:Clo+P20 mg	1 year	MACE, 死亡, MI, 卒中, TVR, Bleeding	4
赵嫣^[15]	2008	中国	60	300/75	G1:Clo+A10 mg G2:Clo+F40 mg	6 months	MACE, 死亡	4
王倩^[16]	2010	中国	100	300/75	G1:Clo+S20 mg G2:Clo+F40 mg	1 month	MACE	4
刘新兵^[17]	2007	中国	102	300/75	G1:Clo+A10-20 mg G2:Clo+P20-40 mg	2 weeks	死亡, MI	4