WARFARIN VS ASPIRIN FOR INTRACRANIAL ARTERIAL STENOSIS

背景和相关性。大动脉粥样硬化性狭窄 在美国，颅内动脉每年导致4万例中风，造成 这个国家每年至少有6亿美元。一直没有 评估这种疾病的最佳药物治疗的前瞻性试验。 这项临床试验的主要目的是比较华法林(INR) 2-3)使用阿司匹林(1300毫克/天)预防中风(缺血性和 症状性狭窄患者的出血性)和血管死亡 一条主要的颅内动脉。研究设计。预期的，随机的， 双盲、多中心试验。所需样本量为403 每组患者(基于33%的中风和血管死亡率 阿司匹林组为3年的百分比，而服用阿司匹林组为22%/3年 华法林组，阿尔法为0.05，贝塔为0.80，停药24% 治疗率和1%的辍学率)。进行审讯。 由以下原因引起的短暂性脑缺血发作(TIA)或中风患者 经血管造影证实的狭窄(大于或等于50%) 一条主要的颅内动脉将随机服用华法林或 阿司匹林。将调整华法林的剂量以维持INR 根据每月的血液测试，在2-3之间。将与患者联系 每月电话检查一次，每四个月检查一次(平均随访3次 年)，以确定是否发生了任何端点。初级阶段 分析将比较中风(缺血性和出血性)和 两个治疗组的血管死亡。二次分析将 比较两个治疗组在i)ALL的比率 血管死亡和致残性中风，二)所有中风(缺血性和 出血性)，三)致命性和非致命性缺血性中风，四)全部缺血性 中风、心肌梗死和血管死亡，v)所有主要系统性疾病 和任何颅内出血，vi)所有的缺血性中风 狭窄的颅内动脉的范围。结论。本研究 将1)确定对有症状的患者的最佳医疗治疗 颅内动脉狭窄，以及2)确定患者的 颅内动脉狭窄范围内的缺血性卒中 最好的医疗方法是足够高(即，大于或等于 到每年6%)，以证明随后的试验比较 颅内血管成形术是这些患者的最佳内科治疗方法。

Background and Relevance. Atherosclerotic stenosis of the major intracranial arteries causes 40,000 strokes per year in the USA, costing the country at least 600,000,000 dollars annually. There have been no prospective trials evaluating optimal medical therapy for this disease. The main objective of this clinical trial is to compare warfarin (INR 2-3) with aspirin (1300 mg/day) for preventing stroke (ischemic and hemorrhagic) and vascular death in patients with symptomatic stenosis of a major intracranial artery. Study Design. Prospective, randomized, double-blind, multi-center trial. The sample size required will be 403 patients per group (based on stroke and vascular death rates of 33 percent/3 years in the aspirin group vs 22 percent/3 years in the warfarin group, an alpha of 0.05, beta of 0.80, a 24 percent withdrawal of therapy rate, and a 1 percent drop out rate). Conduct of Trial. Patients with transient ischemic attack (TIA) or stroke caused by angiographically proven stenosis (greater than or equal to 50 percent) of a major intracranial artery will be randomized to warfarin or aspirin. The dose of warfarin will be adjusted to maintain the INR between 2-3 based on monthly blood tests. Patients will be contacted monthly by phone and examined every four months (mean follow-up of 3 years) to determine whether any endpoints have occurred. The primary analysis will compare the rates of stroke (ischemic and hemorrhagic) and vascular death in the two treatment groups. Secondary analyses will compare the two treatment groups with respect to rates of i) all vascular deaths and disabling stroke, ii) all stroke (ischemic and hemorrhagic), iii) fatal and nonfatal ischemic stroke, iv) all ischemic stroke, myocardial infarction and vascular death, v) all major systemic and any intracranial hemorrhage, vi) all ischemic stroke in the territory of the stenotic intracranial artery. Conclusion. This study will 1) define optimal medical therapy for patients with symptomatic intracranial arterial stenosis, and 2) identify patients whose rate of ischemic stroke in the territory of the stenotic intracranial artery on best medical therapy is sufficiently high (i.e., greater than or equal to 6 percent per year) to justify a subsequent trial comparing intracranial angioplasty with best medical therapy in these patients.