CYP2C19 Loss‐of‐Function Variants Associated With Long‐Term Ischemic Stroke Events During Clopidogrel Treatment in the Chinese Population

作者：Peng Wu, Ziqing Liu, Zijian Tian, Benrui Wu, Jian Shao, Qian Li, Zhaoxu Geng, Ying Pan, Ke Lü, Qiang Wang, Tao Xu, Kaixin Zhou · 发表于：Clinical Pharmacology & Therapeutics · 年份：2023 · DOI：10.1002/cpt.3028 · 被引用次数：11 · 研究领域：Antiplatelet Therapy and Cardiovascular Diseases、Diabetes Treatment and Management、Inflammatory mediators and NSAID effects

This study aims to determine whether CYP2C19 loss-of-function (LoF) variants were associated with long-term ischemic stroke risk in Chinese primary care patients treated with clopidogrel. Patients treated with clopidogrel were ascertained from Chinese electronic medical records linked with a biobank for a retrospective cohort study. Their medical information was examined for the period from January 2018 to December 2021. Two CYP2C19 major loss of function variants (*2:rs4244285 and *3: rs4986893) were genotyped. The clinical outcome was ischemic stroke event. Cox regression analysis was used to evaluate the association between the occurrence of ischemic stroke events and CYP2C19 LoF variants. Covariates included age, gender, body mass index, prior ischemic stroke, transient ischemic attack, hypertension, diabetes mellitus, hyperlipoidemia, smoke status, aspirin use, proton-pump inhibitor use, and statin use. Of the 1,141 patients included in the clopidogrel therapy cohort, 61.9% carried at least one CYP2C19 LoF variant. During a median follow-up period of 12 months, 103 patients (9.0%) had an ischemic stroke. After adjusting for other risk factors, carriers of CYP2C19 LoF variants had significantly higher risk of ischemic stroke compared with non-carriers (hazard ratio: 1.64, 95% confidence interval: 1.06-2.53, P = 0.025). This pharmacogenetic study of clopidogrel provides novel insights into the association between the CYP2C19 LoF variant and long-term stroke risk. We establ...