CYP2C19 Polymorphism and Clopidogrel Efficacy in Long-Term Outcomes of Large-Artery Atherosclerotic Stroke: The NCVC Genome Registry.

JACC. Asia Pub Date : 2025-09-01 DOI:10.1016/j.jacasi.2025.07.020

Takeshi Yoshimoto, Yorito Hattori, Hiroyuki Ishiyama, Yuriko Nakaoku, Soshiro Ogata, Soichiro Abe, Kenji Ninomiya, Kunihiro Nishimura, Masafumi Ihara

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引用次数: 0

Abstract

Background: CYP2C19 polymorphisms influence clopidogrel metabolism, which may influence long-term stroke prognosis.

Objectives: The authors sought to investigate whether CYP2C19 polymorphisms were associated with long-term recurrent ischemic events in patients with acute ischemic stroke due to large-artery atherosclerosis (LAA).

Methods: The present study, comprising a sub-data set from the National Cerebral and Cardiovascular Center Genome Registry-a data registry from a multicenter, prospective, observational study-enrolled patients with LAA stroke within 7 days of stroke onset who consented to genotyping of CYP2C19 polymorphism between 2004 and 2022. Based on CYP2C19 polymorphisms, participants were assigned to 1 of 3 groups: extensive metabolizers (∗1/∗1), intermediate metabolizers (∗1/∗2, ∗1/∗3), and poor metabolizers (∗2/∗2, ∗2/∗3, ∗3/∗3). The primary endpoint was the recurrence of symptomatic ischemic stroke/transient ischemic attack.

Results: Among 369 participants with LAA stroke (96 females [26.0%]; age, median [Q1-Q3], 74 [65-80] years) and a median follow-up of 5.1 years, poor or intermediate metabolizers (PM/IMs) (n = 164) had a significantly higher risk of recurrent symptomatic ischemic stroke transient ischemic attack than extensive metabolizers (n = 205) (adjusted HR: 2.33; 95% CI: 1.28-4.24). Furthermore, restricting the analysis to patients taking clopidogrel, PM/IMs exhibited a similarly significant risk (adjusted HR: 5.26; 95% CI: 1.87-14.56).

Conclusions: In patients with LAA stroke, CYP2C19 PM/IMs had a significantly higher long-term recurrence rate of ischemic events than extensive metabolizers.

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CYP2C19多态性和氯吡格雷对大动脉粥样硬化性卒中长期预后的影响：NCVC基因组登记

背景：CYP2C19多态性影响氯吡格雷代谢，可能影响脑卒中远期预后。目的：作者试图研究CYP2C19多态性是否与大动脉粥样硬化（LAA）急性缺血性卒中患者长期复发性缺血事件相关。方法：本研究包括来自国家脑和心血管中心基因组登记的子数据集，这是一项多中心、前瞻性、观察性研究的数据登记，纳入了2004年至2022年间卒中发作7天内同意进行CYP2C19多态性基因分型的LAA卒中患者。根据CYP2C19多态性，参与者被分配到3组中的1组：广泛代谢者（∗1/∗1），中间代谢者（∗1/∗2,∗1/∗3）和不良代谢者（∗2/∗2,∗2/∗3,∗3/∗3）。主要终点是症状性缺血性卒中/短暂性缺血性发作的复发。结果：在369名LAA卒中参与者中（96名女性[26.0%]，年龄，中位[Q1-Q3]， 74[65-80]岁），中位随访5.1年，不良或中等代谢（PM/IMs）（n = 164）比广泛代谢（n = 205）具有明显更高的复发性症状性缺血性卒中短暂性脑缺血发作的风险（调整HR: 2.33; 95% CI: 1.28-4.24）。此外，将分析限制在服用氯吡格雷的患者中，PM/IMs表现出类似的显著风险（调整后的HR: 5.26; 95% CI: 1.87-14.56）。结论：在LAA脑卒中患者中，CYP2C19 PM/IMs的长期缺血性事件复发率明显高于广泛代谢物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

JACC. Asia Cardiology and Cardiovascular Medicine

CiteScore

4.00

自引率

0.00%

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