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IF 10.5 1区医学 Q1 MEDICINE, GENERAL & INTERNAL

JAMA Network Open Pub Date : 2025-04-01 DOI:10.1001/jamanetworkopen.2025.0398

Yo Han Jung, Tae-Jin Song, Jinkwon Kim, Hee-Kwon Park, Sang Won Han, Young Dae Kim, Jong-Ho Park, Jae-Kwan Cha, Hyun Young Park, Sung-Il Sohn, Sungwook Yu, Jun Hong Lee, Dong Hoon Shin, Eung-Gyu Kim, Hye Sun Lee, Kyung-Yul Lee

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引用次数: 0

摘要

重要性：细胞色素 P450 2C19 (CYP2C19) 基因型会影响氯吡格雷向其活性代谢物的转化，从而影响其抗血小板作用。然而，关于 CYP2C19 基因型对氯吡格雷预防急性缺血性脑卒中患者心血管事件作用的影响，前瞻性试验的证据仍然有限：研究 CYP2C19 基因型与接受氯吡格雷治疗的急性缺血性卒中患者临床预后的关系：2019年9月1日至2023年1月27日，在韩国37个临床研究机构开展了一项前瞻性非随机临床试验。纳入了在急性缺血性脑卒中发生后 72 小时内接受氯吡格雷治疗的患者：通过 CYP2C19 基因分型将患者分为 CYP2C19 功能缺失 (LOF) 等位基因携带者和非携带者。在整个研究期间维持氯吡格雷治疗：主要结果是CYP2C19 LOF等位基因携带者和非携带者患者在缺血性中风后6个月内发生心血管事件（包括缺血性或出血性中风、心肌梗死或心血管死亡）的风险差异。主要安全性结果是全因死亡率和大出血发生率的差异。进行了意向治疗分析：共有2925名患者参加了PLATELET试验。参与者的平均年龄（标清）为 65.3（12.4）岁，男性 1928 人（66.3%）。在这些患者中，有 15 人被排除在外。在剩余的 2910 名患者中，61.3% 被归类为低代谢或中等代谢，38.7% 被归类为高代谢。与非携带者相比，LOF CYP2C19 等位基因携带者的主要结果发生率更高（2.7% [1785 例中的 49 例] vs 1.6% [1125 例中的 18 例]；对数秩 P = .048）。在大出血发生率（0.6% [1785例中的11例] vs 0.8% [1125例中的9例]；P = .56）和全因死亡率（0.3% [5] vs 0.1% [1]；P = .27）方面，CYP2C19 LOF等位基因携带者和非携带者之间未观察到明显差异：在这项前瞻性非随机临床试验中，CYP2C19 LOF等位基因型携带者发生心血管事件的可能性较高：试验注册：ClinicalTrials.gov Identifier：NCT04072705。

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Cytochrome P450 2C19 Genotypes and Clopidogrel in Patients With Ischemic Stroke: A Nonrandomized Clinical Trial.

Importance: Cytochrome P450 2C19 (CYP2C19) genotypes influence the antiplatelet effectiveness of clopidogrel by affecting its conversion to its active metabolite. However, evidence from prospective trials regarding the effects of CYP2C19 genotypes on the role of clopidogrel preventing cardiovascular events among patients with acute ischemic stroke remains limited.

Objective: To investigate the association of the CYP2C19 genotypes with the clinical prognosis of patients with acute ischemic stroke treated with clopidogrel.

Design, setting, and participants: A prospective, nonrandomized clinical trial was conducted from September 1, 2019, to January 27, 2023, at 37 clinical sites in South Korea. Patients who received clopidogrel within 72 hours of experiencing an acute ischemic stroke were included.

Interventions: Patients were classified using CYP2C19 genotyping into carrier and noncarrier of CYP2C19 loss-of-function (LOF) allele. Clopidogrel treatment was maintained throughout the study period.

Main outcomes and measures: The primary outcome was the difference in the risk of cardiovascular events (including ischemic or hemorrhagic stroke, myocardial infarction, or cardiovascular death) within 6 months after an ischemic stroke between patients who were carriers or noncarriers of the CYP2C19 LOF allele. The primary safety outcomes were the differences in all-cause mortality and the occurrence of major bleeding. Intention-to-treat analysis was performed.

Results: Overall, 2925 patients were enrolled in the PLATELET trial. The mean (SD) age of the participants was 65.3 (12.4) years, and 1928 (66.3%) were men. Among these patients, 15 were excluded. Of the remaining 2910 patients, 61.3% were classified as poor or intermediate metabolizers and 38.7% as extensive metabolizers. The primary outcome occurred more frequently in carriers of the LOF CYP2C19 allele than in noncarriers (2.7% [49 of 1785] vs 1.6% [18 of 1125]; log-rank P = .048). No significant differences were observed between CYP2C19 LOF allele carriers and noncarriers regarding the occurrence of major bleeding (0.6% [11 of 1785] vs 0.8% [9 of 1125]; P = .56) and all-cause mortality (0.3% [5] vs 0.1% [1]; P = .27).

Conclusions and relevance: In this prospective nonrandomized clinical trial, carriers of the CYP2C19 LOF allele genotype exhibited a higher likelihood of experiencing cardiovascular events.

Trial registration: ClinicalTrials.gov Identifier: NCT04072705.

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来源期刊

JAMA Network Open Medicine-General Medicine

CiteScore

16.00

自引率

2.90%

发文量

2126

审稿时长

16 weeks

期刊介绍： JAMA Network Open, a member of the esteemed JAMA Network, stands as an international, peer-reviewed, open-access general medical journal.The publication is dedicated to disseminating research across various health disciplines and countries, encompassing clinical care, innovation in health care, health policy, and global health. JAMA Network Open caters to clinicians, investigators, and policymakers, providing a platform for valuable insights and advancements in the medical field. As part of the JAMA Network, a consortium of peer-reviewed general medical and specialty publications, JAMA Network Open contributes to the collective knowledge and understanding within the medical community.