From the Department of Neurology, Stroke Centre, DHU FIRE, INSERM U 1148, Paris Diderot-Sorbonne University, Hôpital Bichat (P.A.), Department of Cardiology, Saint-Antoine Hospital and Medical School, Univeristé Pierre et Marie Curie (A.A.C.), and Department of Biostatistics, Paris-Diderot-Sorbonne University, Hôpital Bichat (C.L.), Assistance Publique-Hôpitaux de Paris, Paris, France; Department of Neurology, Royal Melbourne Hospital (S.D.) and Florey Institute of Neuroscience and Mental Health (D.Y., M.M., G.A.D.), University of Melbourne, Melbourne, Australia; Department of Cardiology, Austin Health, Heidelberg, Victoria, Australia (E.F.J.); Max Planck Institute for Neurological Research, Cologne, Germany (W.-D.H.); Department of Neurology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland (M.K.); Stroke and Ageing Research Centre, Monash University, Melbourne, Australia (D.Y.); and Division of Clinical Neurosciences, University of Edinburgh (SC005336), Scotland, United Kingdom (M.M.).
Stroke. 2014 May;45(5):1248-57. doi: 10.1161/STROKEAHA.113.004251. Epub 2014 Apr 3.
Severe atherosclerosis in the aortic arch is associated with a high risk of recurrent vascular events, but the optimal antithrombotic strategy is unclear.
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.
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.
Because of lack of power, this trial was inconclusive and results should be taken as hypothesis generating.
http://www.clinicaltrials.gov. Unique identifier: NCT00235248.
主动脉弓严重粥样硬化与复发性血管事件风险增加相关，但最佳抗栓策略尚不清楚。
这项前瞻性随机对照、开放标签、终点评估设盲的 PROBE 设计临床试验，旨在比较阿司匹林 75150 mg/d 加氯吡格雷 75 mg/d（A+C）与华法林治疗（国际标准化比值 23）在伴有胸主动脉斑块>4 mm 且无其他明确栓塞源的缺血性卒、短暂性脑缺血发作或外周动脉栓塞患者中的疗效。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。随机分组后 1 个月及之后每 4 个月随访一次。
在 8 年零 3 个月期间共纳入 349 例患者，随后试验提前终止。中位随访 3.4 年后，A+C 组和华法林组分别有 7.6%（13/172）和 11.3%（20/177）的患者发生主要终点事件（对数秩检验，P=0.2）。调整后的风险比为 0.76（95%置信区间，0.361.61；P=0.5）。A+C 组和华法林组分别有 4 例和 6 例患者发生大出血（包括颅内出血）。A+C 组无血管性死亡，而华法林组有 6 例（3.4%）患者发生血管性死亡（对数秩检验，P=0.013）。按国际标准化比值 23 的三分位数进行治疗达标时间（67%时间处于治疗范围内）分析，各组间无显著差异。
由于缺乏统计学效能，本试验结果不确定，只能作为假说产生的依据。
