国家神经系统疾病临床医学研究中心数据管理与共享系统
Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases
Association Between CYP2C19 Loss-of-Function Allele Status and Efficacy of Clopidogrel for Risk Reduction Among Patients With Minor Stroke or Transient Ischemic Attack.
第一作者：Yilong Wang
通讯作者：Yongjun Wang
基本信息
- 负责人：Yilong Wang
- 数据来源： CHANCE
- 论文编号：OTHERS20190375
- 发表时间：2016-07-05
2016-07-05
已发表文章
主要研究背景及目的
方法
Three CYP2C19 major alleles (*2, *3, *17)were genotyped among 2933 Chinese patients from 73 sites whowere enrolled in the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) randomized trial conducted from January 2, 2010, to March 20, 2012. Patients with acute minor ischemic stroke or transient ischemic attack in the trialwere randomized to treatment with clopidogrel combined with aspirin or to aspirin alone. The primary efficacy outcomewas new stroke. The secondary efficacy outcomewas a composite of new composite vascular events (ischemic stroke, hemorrhagic stroke,myocardial infarction, or vascular death). Bleeding was the safety outcome.
结论
Among patients with minor ischemic stroke or transient ischemic attack, the use of clopidogrel plus aspirin compared with aspirin alone reduced the risk of a new stroke only in the subgroup of patients who were not carriers of the CYP2C19 loss-of-function alleles. These findings support a role of CYP2C19 genotype in the efficacy of this treatment.
主要结果
Among 2933 patients, 1948 (66.4%)were men, with a mean age of 62.4 years. Overall, 1207 patients (41.2%)were noncarriers and 1726 patients (58.8%)were carriers of loss-of-function alleles (*2, *3). After day 90follow-up, clopidogrel-aspirin reduced the rate of new stroke in the noncarriers but not in the carriers of the loss-of-function alleles (P =.02 for interaction; events among noncarriers, 41 [6.7%] with clopidogrel-aspirin vs 74 [12.4%] with aspirin; hazard ratio [HR],0.51 [95%CI,0.35-0.75]; events among carriers, 80 [9.4%] with clopidogrel-aspirin vs 94 [10.8%] with aspirin; HR,0.93 [95%CI,0.69 to 1.26]). Similar resultswere observed for the secondary composite efficacy outcome (noncarriers: 41 [6.7%] with clopidogrel-aspirin vs 75 [12.5%] with aspirin; HR,0.50 [95%CI,0.34-0.74]; carriers: 80 [9.4%] with clopidogrel-aspirin vs 95 [10.9%] with aspirin; HR,0.92 [95%CI,0.68-1.24]; P = .02 for interaction). The effect of treatment assignment on bleeding did not vary significantly between the carriers and the noncarriers of the loss-of-function alleles (2.3%for carriers and 2.5%for noncarriers in the clopidogrel-aspirin group vs 1.4%for carriers and 1.7% for noncarriers in the aspirin only group; P = .78 for interaction).