Background and Purpose- The RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) tested the hypothesis that dabigatran would be superior to aspirin for the prevention of recurrent stroke in patients with embolic stroke of undetermined source. This exploratory subgroup analysis investigates the impact of age, renal function (both predefined), and dabigatran dose (post hoc) on the rates of recurrent stroke and major bleeding. Methods- RE-SPECT ESUS was a multicenter, randomized, double-blind trial of dabigatran 150 or 110 mg (for patients aged ≥75 years and/or with creatinine clearance 30 to <50 mL/minute) twice daily compared with aspirin 100 mg once daily. The primary outcome was recurrent stroke. Results- The trial, which enrolled 5390 patients from December 2014 to January 2018, did not demonstrate superiority of dabigatran versus aspirin for prevention of recurrent stroke in patients with embolic stroke of undetermined source. However, among the population qualifying for the lower dabigatran dose, the rate of recurrent stroke was reduced with dabigatran versus aspirin (7.4% versus 13.0%; hazard ratio, 0.57 [95% CI, 0.39-0.82]; interaction P=0.01). This was driven mainly by the subgroup aged ≥75 years (7.8% versus 12.4%; hazard ratio, 0.63 [95% CI, 0.43-0.94]; interaction P=0.10). Stroke rates tended to be lower with dabigatran versus aspirin with declining renal function. Risks for major bleeding were similar between treatments, irrespective of renal function, but with a trend for lower bleeding rates with dabigatran versus aspirin in older patients. Conclusions- In subgroup analyses of RE-SPECT ESUS, dabigatran reduced the rate of recurrent stroke compared with aspirin in patients qualifying for the lower dose of dabigatran. These results are hypothesis-generating. Aspirin remains the standard antithrombotic treatment for patients with embolic stroke of undetermined source. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120.

Biostatistics and Data Sciences Boehringer Ingelheim Pharma GmbH and Co K G Ingelheim Germany

Cardiology Medicine Boehringer Ingelheim International GmbH Germany

Cardiometabolic Medicine Boehringer Ingelheim Ltd Burlington ON Canada

Center of Neurology and Neurosurgery Goethe University Frankfurt Frankfurt am Main Germany

Clinical and Translational Science Miller School of Medicine University of Miami FL

Clinical Operations Global Boehringer Ingelheim Pharma GmbH and Co K G Biberach Germany

Comprehensive Stroke Center Department of Neurology Palacky University Olomouc Czech Republic

Department of Neurology Cerebrovaskulární ambulance s r o Brno Czech Republic

Department of Neurology Department of Surgery and Perioperative Care Seton Dell Medical School Stroke Institute Austin TX

Department of Neurology Evangelisches Klinikum Bethel Bielefeld Germany

Department of Neurology Melbourne Brain Centre University of Melbourne Parkville VIC Australia

Department of Neurology Morsani College of Medicine University of South Florida Tampa

Department of Neurology Northwestern University Chicago IL

Department of Neurology Pavol Jozef Šafárik University in Košice University Hospital L Pasteur Košice Slovak Republic

Department of Neurology Royal Adelaide Hospital Adelaide South Australia Australia

Department of Neurology University Hospital Ostrava Ostrava Poruba Poruba Czech Republic

Department of Neurology University of California San Francisco

Department of Neurology with Focus on Neurovascular Diseases and Neurooncology University of Tübingen and Hertie Institute for Clinical Brain Research Germany

Department of Neurosciences and Preventive Medicine Danube University Krems Krems an der Donau Austria

Division of Neurology Stroke Center University Hospital Basel Switzerland

Duke Clinical Research Institute Duke University Medical Center Durham NC

Faculty of Medicine Mannheim of the University of Heidelberg Germany

From the Faculty of Medicine Institute for Medical Informatics Biometry and Epidemiology University Duisburg Essen Germany

Metabolism Medicine Boehringer Ingelheim International GmbH Germany

Neurology Service Hospital de Clínicas de Porto Alegre Brazil

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ClinicalTrials.gov
NCT02239120