Hans-Christoph Diener1, Ralph L Sacco1, J Donald Easton1, Christopher B Granger1, Richard A Bernstein1, Shinichiro Uchiyama1, Jörg Kreuzer1, Lisa Cronin1, Daniel Cotton1, Claudia Grauer1, Martina Brueckmann1, Marina Chernyatina1, Geoffrey Donnan1, José M Ferro1, Martin Grond1, Bernd Kallmünzer1, Jerzy Krupinski1, Byung-Chul Lee1, Robin Lemmens1, Jaime Masjuan1, Miroslav Odinak1, Jeffrey L Saver1, Peter D Schellinger1, Danilo Toni1, Kazunori Toyoda1. 1. 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.).
Abstract
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) oraspirin (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.).
RCT Entities:
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.).
Authors: Niraj Varma; Iwona Cygankiewicz; Mintu P Turakhia; Hein Heidbuchel; Yu-Feng Hu; Lin Yee Chen; Jean-Philippe Couderc; Edmond M Cronin; Jerry D Estep; Lars Grieten; Deirdre A Lane; Reena Mehra; Alex Page; Rod Passman; Jonathan P Piccini; Ewa Piotrowicz; Ryszard Piotrowicz; Pyotr G Platonov; Antonio Luiz Ribeiro; Robert E Rich; Andrea M Russo; David Slotwiner; Jonathan S Steinberg; Emma Svennberg Journal: Circ Arrhythm Electrophysiol Date: 2021-02-12
Authors: James E Siegler; Jesse M Thon; John H Woo; David Do; Steven R Messé; Brett Cucchiara Journal: J Stroke Cerebrovasc Dis Date: 2019-07-26 Impact factor: 2.136
Authors: Victor J Del Brutto; Seemant Chaturvedi; Hans-Christoph Diener; Jose G Romano; Ralph L Sacco Journal: J Am Coll Cardiol Date: 2019-08-13 Impact factor: 24.094