Efficacy of clopidogrel for stroke depends on CYP2C19 genotype and risk profile
Efficacy of clopidogrel for stroke depends on CYP2C19 genotype and risk profile
复制标题
氯吡格雷治疗中风的疗效取决于 CYP2C19 基因型和风险状况。
DOI：
10.1002/ana.25535
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发表时间：
2019-09-01
影响因子：
11.2
通讯作者：
Wang, Yongjun
中科院分区：
文献类型：
--
作者：
Xu, Jie;Wang, Anxin;Wang, Yongjun
目的美国心脏协会/美国卒中协会指南建议对轻度脑卒中（MS）和短暂性脑缺血发作（TIA）患者采用氯吡格雷联合阿司匹林的双联抗血小板治疗（DAT）。本研究的目的是找到潜在的亚组，受益于DAT。我们的目的是比较氯吡格雷-阿司匹林治疗的疗效与阿司匹林治疗MS/TIA患者分层的CYP 2C 19基因型和风险概况。方法CYP 2C 19功能丧失等位基因（LoFA）携带者定义为LoFA为 *2或 *3的患者。低风险和高风险特征分别定义为埃森卒中风险评分（ESRS）= 3。1年时卒中复发被视为主要结局。结果在2,933例MS/TIA患者中，有1,726例（58.8%）为LoFA携带者，1,068例（36.4%）为高危患者（ESRS ≥ 3）。在LoFA携带者中，氯吡格雷联合阿司匹林组与阿司匹林单药组的卒中复发率无显著性差异（11.2%vs 13.3%，HR = 0.83，95%CI = 0.64~1.09）。在按CYP 2C 19基因型和ESRS分层分析中，氯吡格雷-阿司匹林治疗卒中复发的HR（95% CI）为1.00（0.70~1.42），0.63（0.41~0.97），0.62（0.40~0.96）和0.52 LoFA携带者低危、LoFA携带者高危、LoFA非携带者低危、LoFA非携带者高危亚组间差异分别为（0.31~0.88），相互作用的p = 0.021。总体而言，LoFA携带者不会从DAT中受益，但对于高风险的LoFA携带者有显著的益处。氯吡格雷在中国MS/TIA患者中的获益取决于CYP 2C 19基因型和风险特征。神经网络2019;86：419-426
Objective Dual antiplatelet therapy (DAT) with clopidogrel plus aspirin has been suggested by American Heart Association/American Stroke Association guidelines for minor stroke (MS) and transient ischemic attack (TIA) patients. The purpose of this study was to find the potential subgroups that benefit from DAT. We aimed to compare the efficacy of clopidogrel-aspirin therapy with that of aspirin therapy in MS/TIA patients stratified by CYP2C19 genotype and risk profiles. Methods CYP2C19 loss-of-function allele (LoFA) carriers were defined as patients with LoFA of either *2 or *3. Low- and high-risk profile was defined as Essen Stroke Risk Score (ESRS) = 3, respectively. Stroke recurrence at 1 year was considered primary outcome. Results Of a total 2,933 MS/TIA patients, there were 1,726 (58.8%) LoFA carriers and 1,068 (36.4%) patients at high risk (ESRS >= 3). No significant difference for stroke recurrence between the clopidogrel-aspirin group and aspirin alone group was found in LoFA carriers (11.2% vs 13.3%, hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.64~1.09). In stratified analyses by CYP2C19 genotype and ESRS, HRs (95% CIs) of the clopidogrel-aspirin therapy for stroke recurrence were 1.00 (0.70~1.42), 0.63 (0.41~0.97), 0.62 (0.40~0.96), and 0.52 (0.31~0.88) among subgroups of LoFA carriers at low risk, LoFA carriers at high risk, LoFA noncarriers at low risk, and LoFA noncarriers at high risk, respectively, with p = 0.021 for interaction. Interpretation Overall, LoFA carriers do not benefit from DAT, but there is significant benefit for LoFA carriers who are at high risk. The benefit of clopidogrel in Chinese MS/TIA patients depends on CYP2C19 genotype and risk profile. ANN NEUROL 2019;86:419-426