The Influence of CYP2C19 Polymorphism on Antiplatelet Effects and Clinical Outcomes in Non-acute Stroke Patients Treated With Clopidogrel: The Contribution of Genetic Analysis to the Efficacy of Clopidogrel (Cognac) Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 518
- 主要终点
- The primary outcome of the study was recurrent cardiovascular event (CVEs), including ischemic stroke, transient ischemic attack (TIA), acute myocardial infarction, urgent revascularization, other thromboembolic disease, and cardiovascular death.
研究概览
简要总结
Background:
Clopidogrel, an antiplatelet prodrug, is widely used for prevention of the recurrent cardiovascular events. CYP2C19 is one of the crucial enzymes for the activation of clopidogrel. Recent studies, mostly done in cardiovascular patients, showed association of the CYP2C19 genotypes with recurrent cardiovascular events. However, prospective data on the impact of the genetic variants in stroke patients are limited.
Methods:
Five hundred and eighteen Japanese non-acute stroke patients treated with clopidogrel were registered at 14 institutions. Three CYP2C19 variants (CYP2C19*2, *3, *17) were genotyped and the patients were classified into three clopidogrel metabolizer groups inferred from the CYP2C19 genotypes: extensive (EM: *1/*1), intermediate (IM: *1/*2 or *1/*3), and poor (PM: *2/*2, *2/*3, or *3/*3). The CYP2C19*17 carriers were excluded from the analysis. The antiplatelet effects of clopidogrel were assessed by Adenosine diphosphate (ADP) -induced platelet aggregation and vasodilator-stimulated phosphoprotein (VASP) phosphorylation, expressed as VASP index. The endpoint was the composite incidence of stroke, transient ischemic attack, myocardial infarction, revascularization, other thromboembolic disease, or cardiovascular death during 2 years of follow-up.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who had received long-term clopidogrel therapy (once a day for at least one month) with a minimum one-month interval between enrollment and the last cerebral ischemic or TIA event.
- •Males and females aged 20 years or older who were prescribed clopidogrel for the secondary prevention of cerebral infarction or transient ischemic attack and who were willing and able to give written informed consent.
排除标准
- •Malignancies
- •Congenital bleeding tendency
- •Atrial fibrillation
- •Concomitant use of an oral anticoagulant agent
- •a platelet count of < 100 x 109/L or > 450 x 109/L within 3 months of enrollment
- •Modified rankin scale > 4
结局指标
主要结局
The primary outcome of the study was recurrent cardiovascular event (CVEs), including ischemic stroke, transient ischemic attack (TIA), acute myocardial infarction, urgent revascularization, other thromboembolic disease, and cardiovascular death.
时间窗: Two Years
Ischemic stroke was defined as a new neurologic deficit of cardiovascular origin lasting at least \> 24 hours based on radiological evidence of stroke. TIA was defined as a transient episode of neurologic dysfunction caused by focal brain ischemia and improving within 24 hours. Urgent revascularization was defined as emergent revascularization for unexpected hospitalization. Acute myocardial infarction was defined as myocardial cell necrosis in the setting of ischemic symptoms and electrocardiogram changes (ST segment elevation or depression, development of Q waves) and/or rising specific cardiac biomarkers. Cardiovascular death was defined as death due to stroke, myocardial infarction or documented sudden cardiac death.
次要结局
- Secondary outcome was major bleeding (intracranial haemorrhage, documented retroperitoneal bleed, and any red blood cell transfusion rates or proportion with bleeding associated with a ≧2g/dl hemoglobin drop).(two years)
研究者
Tomotaka Tanaka
Medical Researcher, Department of Neurology
National Cerebral and Cardiovascular Center, Japan