• Hans-Christoph Diener, Ralph L Sacco, J Donald Easton, Christopher B Granger, Richard A Bernstein, Shinichiro Uchiyama, Jörg Kreuzer, Lisa Cronin, Daniel Cotton, Claudia Grauer, Martina Brueckmann, Marina Chernyatina, Geoffrey Donnan, José M Ferro, Martin Grond, Bernd Kallmünzer, Jerzy Krupinski, Byung-Chul Lee, Robin Lemmens, Jaime Masjuan, Miroslav Odinak, Jeffrey L Saver, Peter D Schellinger, Danilo Toni, Kazunori Toyoda, and RE-SPECT ESUS Steering Committee and Investigators.
• 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.).
• N. Engl. J. Med. 2019 May 16; 380 (20): 1906-1917.

BackgroundCryptogenic 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.MethodsWe 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.ResultsA 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.ConclusionsIn 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.).Copyright © 2019 Massachusetts Medical Society.

29 keywords...

hide…