达比加群酯预防来源不明的栓塞性卒中后卒中
Dabigatran for Prevention of Stroke after Embolic Stroke of Undetermined Source.
机构信息
From the University Duisburg-Essen and University Hospital Essen, Essen (H.-C.D.), Boehringer Ingelheim Pharma GmbH K.G., Biberach (C.G.), Boehringer Ingelheim International GmbH, Ingelheim, Faculty of Medicine Mannheim of the University of Heidelberg, Mannheim (M.B.), Kreisklinikum Siegen, Siegen, and the University of Marburg, Marburg (M.G.), University Hospital Erlangen, Erlangen (B.K.), and Johannes Wesling Klinikum Minden and Ruhr University Bochum, Minden (P.D.S.) - all in Germany; Miller School of Medicine, University of Miami, Miami (R.L.S.); University of California at San Francisco, San Francisco (J.D.E.), and the Department of Neurology and Comprehensive Stroke Center, University of California at Los Angeles, Los Angeles (J.L.S.) - both in California; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (C.B.G.); Feinberg School of Medicine of Northwestern University, Chicago (R.A.B.); International University of Health and Welfare, Center for Brain and Cerebral Vessels, Sanno Hospital and Sanno Medical Center, Tokyo (S.U.), and the National Cerebral and Cardiovascular Center, Osaka (K.T.) - both in Japan; Boehringer Ingelheim, Singapore, Singapore (J. Kreuzer); Boehringer Ingelheim, Burlington, ON, Canada (L.C.); Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (D.C.); City Clinical Emergency Care Hospital, Kursk (M.C.), and the Military Medical Academy, St. Petersburg (M.O.) - both in Russia; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia (G.D.); Serviço de Neurologia, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Instituto de Medicina Molecular, University of Lisbon, Lisbon, Portugal (J.M.F.); F. Ass. Mutua Terrassa, Terrassa (J. Krupinski), and Servicio de Neurología, Hospital Universitario Ramón y Cajal (IRYCIS), Departamento de Medicina, Universidad de Alcalá, Madrid (J.M.) - both in Spain; Hallym University Sacred Heart Hospital, Seoul, South Korea (B.-C.L.); KU Leuven-University of Leuven, Department of Neurosciences, Experimental Neurology, VIB Center for Brain & Disease Research, University Hospitals Leuven, Department of Neurology, Leuven, Belgium (R.L.); and Hospital Policlinico Umberto I, Sapienza University, Rome (D.T.).
出版信息
N Engl J Med. 2019 May 16;380(20):1906-1917. doi: 10.1056/NEJMoa1813959.
BACKGROUND
Cryptogenic strokes constitute 20 to 30% of ischemic strokes, and most cryptogenic strokes are considered to be embolic and of undetermined source. An earlier randomized trial showed that rivaroxaban is no more effective than aspirin in preventing recurrent stroke after a presumed embolic stroke from an undetermined source. Whether dabigatran would be effective in preventing recurrent strokes after this type of stroke was unclear.
METHODS
We conducted a multicenter, randomized, double-blind trial of dabigatran at a dose of 150 mg or 110 mg twice daily as compared with aspirin at a dose of 100 mg once daily in patients who had had an embolic stroke of undetermined source. The primary outcome was recurrent stroke. The primary safety outcome was major bleeding.
RESULTS
A total of 5390 patients were enrolled at 564 sites and were randomly assigned to receive dabigatran (2695 patients) or aspirin (2695 patients). During a median follow-up of 19 months, recurrent strokes occurred in 177 patients (6.6%) in the dabigatran group (4.1% per year) and in 207 patients (7.7%) in the aspirin group (4.8% per year) (hazard ratio, 0.85; 95% confidence interval [CI], 0.69 to 1.03; P = 0.10). Ischemic strokes occurred in 172 patients (4.0% per year) and 203 patients (4.7% per year), respectively (hazard ratio, 0.84; 95% CI, 0.68 to 1.03). Major bleeding occurred in 77 patients (1.7% per year) in the dabigatran group and in 64 patients (1.4% per year) in the aspirin group (hazard ratio, 1.19; 95% CI, 0.85 to 1.66). Clinically relevant nonmajor bleeding occurred in 70 patients (1.6% per year) and 41 patients (0.9% per year), respectively.
CONCLUSIONS
In patients with a recent history of embolic stroke of undetermined source, dabigatran was not superior to aspirin in preventing recurrent stroke. The incidence of major bleeding was not greater in the dabigatran group than in the aspirin group, but there were more clinically relevant nonmajor bleeding events in the dabigatran group. (Funded by Boehringer Ingelheim; RE-SPECT ESUS ClinicalTrials.gov number, NCT02239120.).
背景
不明来源的缺血性中风占 20%至 30%，大多数不明来源的中风被认为是栓塞性和来源不明的。 一项早期的随机试验表明，利伐沙班在预防来源不明的栓塞性中风后复发方面并不优于阿司匹林。 在这种类型的中风后，达比加群是否能有效预防中风复发尚不清楚。
方法
我们进行了一项多中心、随机、双盲试验，比较了达比加群（150 毫克或 110 毫克，每日两次）与阿司匹林（100 毫克，每日一次）在不明来源栓塞性中风患者中的疗效。 主要结局是中风复发。 主要安全性结局是大出血。
结果
共有 5390 名患者在 564 个地点入组，随机分为达比加群组（2695 名患者）或阿司匹林组（2695 名患者）。 在中位随访 19 个月期间，达比加群组 177 例（6.6%）患者发生中风复发（4.1%/年），阿司匹林组 207 例（7.7%）患者发生中风复发（4.8%/年）（风险比，0.85；95%置信区间[CI]，0.69 至 1.03；P=0.10）。 缺血性中风分别发生在 172 例（4.0%/年）和 203 例（4.7%/年）患者中（风险比，0.84；95%CI，0.68 至 1.03）。 达比加群组 77 例（1.7%/年）和阿司匹林组 64 例（1.4%/年）发生大出血（风险比，1.19；95%CI，0.85 至 1.66）。 达比加群组 70 例（1.6%/年）和阿司匹林组 41 例（0.9%/年）发生临床相关非大出血。
结论
在近期不明来源栓塞性中风患者中，达比加群在预防中风复发方面并不优于阿司匹林。 达比加群组大出血发生率不比阿司匹林组高，但达比加群组临床相关非大出血事件更多。 （由勃林格殷格翰公司资助；RE-SPECT ESUS ClinicalTrials.gov 编号，NCT02239120）。
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