Impact of CYP2C19 Genotype on Efficacy and Safety of Clopidogrel-based Antiplatelet Therapy in Stroke or Transient Ischemic Attack Patients: An Updated Systematic Review and Meta-analysis of Non-East Asian Studies.

IF 3.1 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Drugs and Therapy Pub Date : 2024-12-01 Epub Date: 2023-12-01 DOI:10.1007/s10557-023-07534-0

Sarah Cargnin, Federica Ferrari, Salvatore Terrazzino

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引用次数: 0

Abstract

Purpose: Inconclusive and limited results have been reported on the clinical utility of CYP2C19 genotyping in stroke/TIA patients of non-East Asian ancestries. We herein performed an updated systematic review and meta-analysis to quantitatively estimate the association of CYP2C19 loss-of function (LOF) status with efficacy and safety of clopidogrel-based antiplatelet therapy in non-East Asian patients affected by stroke or TIA.

Methods: A comprehensive search was performed up to July 2023 using PubMed, Web of Knowledge, and Cochrane Library databases. The clinical outcomes investigated were stroke, composite vascular events and bleeding. Pooled estimates were calculated as risk ratios (RR) with 95% CI using the Mantel- Haenszel random-effects model. The quality of evidence was assessed using the GRADEpro tool.

Results: A total number of 1673 stroke/TIA patients from 8 non-East Asian studies, published between 2014 and 2022, were included in the systematic review. Clopidogrel-treated carriers of CYP2C19 LOF alleles were found at increased risk of stroke compared to non-carriers (RR: 1.68, 95%CI: 1.04-2.71, P = 0.03). However, no significant association was observed with the risk of composite vascular events (RR: 1.15, 95%CI: 0.58-2.28, P = 0.69) or bleeding (RR: 0.84, 95%CI: 0.38-1.86, P = 0.67). Similarly, European ancestry patients carrying CYP2C19 LOF alleles displayed a higher risk of stroke (RR: 2.69 (1.11-6.51, P = 0.03), but not of composite vascular events or bleeding.

Conclusion: The present updated meta-analysis provides moderate quality evidence of association between CYP2C19 LOF alleles and an increased risk of stroke in non-East Asian patients with stroke/TIA after receiving clopidogrel therapy. Further large pharmacogenetic studies are still warranted to corroborate these findings.

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CYP2C19基因型对基于氯吡格雷的抗血小板治疗卒中或短暂性脑缺血发作患者疗效和安全性的影响:一项更新的非东亚研究的系统回顾和荟萃分析

目的:CYP2C19基因分型在非东亚血统卒中/TIA患者中的临床应用尚不确定且结果有限。在此，我们进行了一项最新的系统回顾和荟萃分析，以定量评估CYP2C19功能丧失(LOF)状态与基于氯吡格雷的抗血小板治疗在卒中或TIA影响的非东亚患者中的有效性和安全性之间的关系。方法:综合检索PubMed、Web of Knowledge和Cochrane Library数据库，检索截止到2023年7月。研究的临床结果为脑卒中、复合血管事件和出血。使用Mantel- Haenszel随机效应模型计算合并估计为95% CI的风险比(RR)。使用GRADEpro工具评估证据质量。结果:来自2014年至2022年间发表的8项非东亚研究的1673例卒中/TIA患者被纳入系统评价。经氯吡格雷治疗的CYP2C19 LOF等位基因携带者卒中风险高于非携带者(RR: 1.68, 95%CI: 1.04-2.71, P = 0.03)。然而，没有观察到与复合血管事件(RR: 1.15, 95%CI: 0.58-2.28, P = 0.69)或出血(RR: 0.84, 95%CI: 0.38-1.86, P = 0.67)的风险有显著关联。同样，携带CYP2C19 LOF等位基因的欧洲血统患者中风的风险更高(RR: 2.69 (1.11-6.51, P = 0.03)，但复合血管事件或出血的风险不高。结论:目前更新的荟萃分析提供了CYP2C19 LOF等位基因与接受氯吡格雷治疗的非东亚卒中/TIA患者卒中风险增加之间关联的中等质量证据。进一步的大型药物遗传学研究仍有必要证实这些发现。

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来源期刊

Cardiovascular Drugs and Therapy 医学-心血管系统

CiteScore

8.30

自引率

0.00%

发文量

110

审稿时长

4.5 months

期刊介绍： Designed to objectively cover the process of bench to bedside development of cardiovascular drug, device and cell therapy, and to bring you the information you need most in a timely and useful format, Cardiovascular Drugs and Therapy takes a fresh and energetic look at advances in this dynamic field. Homing in on the most exciting work being done on new therapeutic agents, Cardiovascular Drugs and Therapy focusses on developments in atherosclerosis, hyperlipidemia, diabetes, ischemic syndromes and arrhythmias. The Journal is an authoritative source of current and relevant information that is indispensable for basic and clinical investigators aiming for novel, breakthrough research as well as for cardiologists seeking to best serve their patients. Providing you with a single, concise reference tool acknowledged to be among the finest in the world, Cardiovascular Drugs and Therapy is listed in Web of Science and PubMed/Medline among other abstracting and indexing services. The regular articles and frequent special topical issues equip you with an up-to-date source defined by the need for accurate information on an ever-evolving field. Cardiovascular Drugs and Therapy is a careful and accurate guide through the maze of new products and therapies which furnishes you with the details on cardiovascular pharmacology that you will refer to time and time again.