CYP3A4基因多态性对心脑血管疾病患者氯吡格雷响应影响的Meta分析

doi:10.5246/jcps.2021.09.064

中国药学(英文版) ›› 2021, Vol. 30 ›› Issue (9): 762-772.DOI: 10.5246/jcps.2021.09.064

• 【药事管理与临床药学专栏】 • 上一篇下一篇

CYP3A4基因多态性对心脑血管疾病患者氯吡格雷响应影响的Meta分析

覃思蓓¹^,², 贾彤², 扶宇², 李俊蕾², 张欣怡², 祝春素², 梁广楷², 聂小燕²^,^*(), 史录文², 崔一民¹^,²^,^*()

1. 北京大学第一医院药剂科, 北京 100034
2. 北京大学医学部药学院药事管理与临床药学系, 北京 100191

收稿日期:2021-01-21 修回日期:2021-03-15 接受日期:2021-03-24 出版日期:2021-09-27 发布日期:2021-09-27
通讯作者: 聂小燕, 崔一民
作者简介:
+ Tel.: +86-10-83572211, E-mail: cuiymzy@126.com
+ Tel.: +86-10-82805020, E-mail: niexy@bjmu.edu.cn
基金资助:
National Natural Science Foundation of China (Grant No. 81803497).

Association between CYP3A4 gene polymorphisms and clopidogrel response in patients with cardio-cerebrovascular diseases: a systematic review and Meta-analysis

Sibei Qin¹^,², Tong Jia², Yu Fu², Junlei Li², Xinyi Zhang², Chunsu Zhu², Guangkai Liang², Xiaoyan Nie²^,^*(), Luwen Shi², Yimin Cui¹^,²^,^*()

1 Department of Pharmacy, Peking University First Hospital, Beijing 100034, China
2 Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2021-01-21 Revised:2021-03-15 Accepted:2021-03-24 Online:2021-09-27 Published:2021-09-27
Contact: Xiaoyan Nie, Yimin Cui

摘要/Abstract

摘要：

氯吡格雷是目前使用最广泛的P2Y12受体抑制剂之一。CYP3A4在氯吡格雷肝脏代谢中起重要作用。因此,CYP3A4基因多态性或许对服用氯吡格雷治疗的心脑血管疾病患者预测氯吡格雷疗效起重要作用。本研究对CYP3A4基因多态性对心脑血管疾病患者氯吡格雷响应的影响进行meta分析。对2019年10月7日之前发表在Pubmed、Embase、Cochrane Library、clinicaltrail.gov、中国知网(CNKI)、万方数据库上的文献进行系统性检索, 纳入评价CYP3A4不同突变型患者的血小板反应性与临床结局的队列研究或病例对照研究。使用Review Manager软件进行数据分析, 使用NOS量表评价纳入文献的质量。总共纳入18篇文献进行Meta分析。Meta分析结果显示,CYP3A4基因多态性对心脑血管疾病患者服用氯吡格雷后的血小板反应性无显著影响。同时,CYP3A4基因多态性对心脑血管疾病患者长期服用氯吡格雷后的结局无显著影响。

关键词: 氯吡格雷, CYP3A4, Meta分析

Abstract:

CYP3A4 plays a critical role in clopidogrel activation in the liver. The polymorphism ofCYP3A4 may have an important effect on clopidogrel response in patients with cardio-cerebrovascular diseases. We conducted a systematic review and meta-analysis to evaluate the impact ofCYP3A4 polymorphism on platelet reactivity after clopidogrel treatment and the outcomes of patients. A systematic literature search (up to 7^th October, 2019) was performed on the PubMed, EMBASE, Cochrane Library, clinicaltrials.gov, and Chinese databases, including China National Knowledge Infrastructure (CNKI) and Wan Fang Data. Cohort studies or case-control studies evaluated platelet reactivity and patients’ outcomes in different genotype patients. The Review Manager software was used for data analysis, and the NOS scale was used to assess the quality of included studies. A total of 18 articles were included in the Meta-analysis. The results showed the platelet reactivity after clopidogrel administration had no significant difference betweenCYP3A4 variant carriers and non-carriers. The occurrence of composite ischemic events or stent thrombosis had no significant difference betweenCYP3A4 variant carriers and non-carriers, either. In conclusion, there was no significant association betweenCYP3A4 polymorphism and clopidogrel response in patients with cardio-cerebrovascular diseases.

Key words: Clopidogrel, CYP3A4, Meta-analysis

Supporting:

覃思蓓, 贾彤, 扶宇, 李俊蕾, 张欣怡, 祝春素, 梁广楷, 聂小燕, 史录文, 崔一民. CYP3A4基因多态性对心脑血管疾病患者氯吡格雷响应影响的Meta分析[J]. 中国药学(英文版), 2021, 30(9): 762-772.

Sibei Qin, Tong Jia, Yu Fu, Junlei Li, Xinyi Zhang, Chunsu Zhu, Guangkai Liang, Xiaoyan Nie, Luwen Shi, Yimin Cui. Association between CYP3A4 gene polymorphisms and clopidogrel response in patients with cardio-cerebrovascular diseases: a systematic review and Meta-analysis[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(9): 762-772.

图/表 8

Figure 1. Flow chart of study search.

Table 1. Characteristics of the 18 studies included in the Meta-analysis.

Figure 2. Forest plot demonstrating trough CR.

Figure 3. The funnel plot demonstrating the bias of meta-analysis to CR.

Figure 4. Forest plot demonstrating trough PRU.

Figure 5. Forest plot demonstrating trough composite ischemic events.

Figure 6. The funnel plot demonstrating the bias of meta-analysis to composite ischemic events.

Figure 7. Forest plot demonstrating trough recurrent stent thrombosis.

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CYP3A4基因多态性对心脑血管疾病患者氯吡格雷响应影响的Meta分析

Association between CYP3A4 gene polymorphisms and clopidogrel response in patients with cardio-cerebrovascular diseases: a systematic review and Meta-analysis

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