Clopidogrel Plus Aspirin Versus Warfarin in Patients With Stroke and Aortic Arch Plaques
Clopidogrel Plus Aspirin Versus Warfarin in Patients With Stroke and Aortic Arch Plaques
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DOI：
10.1161/strokeaha.113.004251
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发表时间：
2014-05-01
期刊：
影响因子：
8.3
通讯作者：
Donnan, Geoffrey A.
中科院分区：
文献类型：
--
作者：
Amarenco, Pierre;Davis, Stephen;Donnan, Geoffrey A.
背景和目的主动脉弓严重动脉粥样硬化与血管事件复发的高风险相关，但最佳抗血栓策略尚不清楚。方法：本前瞻性随机对照、开放标记试验，采用盲法终点评价（PROBE设计），检验了在缺血性卒中、短暂性脑缺血发作或胸主动脉外周栓塞伴斑块40mm且无其他栓塞源的患者中，阿司匹林75 ~ 150mg /d +氯吡格雷75mg /d （A+C）治疗优于华法林治疗（国际标准化比值2-3）。主要终点包括脑梗死、心肌梗死、外周栓塞、血管性死亡或颅内出血。随机化后1个月随访一次，然后每4个月随访一次。结果在8年零3个月的时间里，349名患者被随机分配后，试验停止。中位随访3.4年后，a +C组和华法林组的主要终点分别为7.6%（13/172）和11.3% (20/177)（log-rank， P=0.2）。校正后的风险比为0.76（95%可信区间为0.36-1.61；P=0.5）。A+C组出现颅内大出血4例，华法林组出现颅内大出血6例。A+C组0例患者发生血管死亡，华法林组6例（3.4%）患者发生血管死亡（log-rank， P=0.013）。治疗范围内的时间（67%的时间为国际标准化比率2-3）按位数分析各组间无显著差异。结论由于缺乏权力，本试验是不确定的，结果应作为假设产生。临床试验注册网址：http://www.clinicaltrials.gov。唯一标识符：NCT00235248。
Background and Purpose Severe atherosclerosis in the aortic arch is associated with a high risk of recurrent vascular events, but the optimal antithrombotic strategy is unclear.Methods This prospective randomized controlled, open-labeled trial, with blinded end point evaluation (PROBE design) tested superiority of aspirin 75 to 150 mg/d plus clopidogrel 75 mg/d (A+C) over warfarin therapy (international normalized ratio 2-3) in patients with ischemic stroke, transient ischemic attack, or peripheral embolism with plaque in the thoracic aorta >4 mm and no other identified embolic source. The primary end point included cerebral infarction, myocardial infarction, peripheral embolism, vascular death, or intracranial hemorrhage. Follow-up visits occurred at 1 month and then every 4 months post randomization.Results The trial was stopped after 349 patients were randomized during a period of 8 years and 3 months. After a median follow-up of 3.4 years, the primary end point occurred in 7.6% (13/172) and 11.3% (20/177) of patients on A+C and on warfarin, respectively (log-rank, P=0.2). The adjusted hazard ratio was 0.76 (95% confidence interval, 0.36-1.61; P=0.5). Major hemorrhages including intracranial hemorrhages occurred in 4 and 6 patients in the A+C and warfarin groups, respectively. Vascular deaths occurred in 0 patients in A+C arm compared with 6 (3.4%) patients in the warfarin arm (log-rank, P=0.013). Time in therapeutic range (67% of the time for international normalized ratio 2-3) analysis by tertiles showed no significant differences across groups.Conclusions Because of lack of power, this trial was inconclusive and results should be taken as hypothesis generating.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00235248.