Rivaroxaban for stroke prevention after embolic stroke of undetermined source

Research output: Contribution to journalArticle


BACKGROUND Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin. METHODS We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source.The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding. RESULTS A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban.The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P = 0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P<0.001). CONCLUSIONS Rivaroxaban was not superior to aspirin with regard to the prevention of recurrent stroke after an initial embolic stroke of undetermined source and was associated with a higher risk of bleeding.


  • R. G. Hart
  • M. Sharma
  • H. Mundl
  • S. E. Kasner
  • S. I. Bangdiwala
  • S. D. Berkowitz
  • B. Swaminathan
  • P. Lavados
  • Y. Wang
  • Y. Wang
  • A. Davalos
  • N. Shamalov
  • R. Mikulik
  • L. Cunha
  • A. Arauz
  • W. Lang
  • A. Czlonkowska
  • J. Eckstein
  • R. J. Gagliardi
  • P. Amarenco
  • S. F. Ameriso
  • T. Tatlisumak
  • R. Veltkamp
  • G. J. Hankey
  • D. Toni
  • D. Bereczki
  • S. Uchiyama
  • G. Ntaios
  • B. W. Yoon
  • R. Brouns
  • M. Endres
  • K. W. Muir
  • N. Bornstein
  • S. Ozturk
  • M. J. O'Donnell
  • M. M. De Vries Basson
  • G. Pare
  • C. Pater
  • B. Kirsch
  • P. Sheridan
  • G. Peters
  • J. I. Weitz
  • W. F. Peacock
  • A. Shoamanesh
  • O. R. Benavente
  • C. Joyner
  • E. Themeles
  • S. J. Connolly
External organisations
  • Bayer Pharma AG
  • University of Pennsylvania
  • McMaster University
  • Bayer Corporation, USA
  • Population Health Research Institute, Ontario
  • Clínica Alemana De Santiago
  • Beijing Tiantan Hospital
  • Autonomous University of Barcelona
  • Pirogov Russian National Research Medical University (RNRMU)
  • St. Anne's University Hospital Brno
  • University Hospital of Coimbra
  • Instituto Nacional de Neurología y Neurocirugía
  • Sigmund Freud Private University
  • Medical University of Warsaw
  • University Hospital Basel
  • Irmandade da Santa Casa de Misericordia de Sao Paulo
  • Hopital Bichat-Claude-Bernard AP-HP
  • Fundacion Para La Lucha Contra Las Enfermedades Neurologicas de La Infancia (FLENI)
  • Sahlgrenska Academy
  • Helsinki University Central Hospital
  • Imperial College London
  • University of Western Australia, Crawley
  • Sapienza University of Rome
  • Semmelweis University
  • International University of Health and Welfare
  • University of Thessaly
  • Seoul National University Hospital
  • Vrije Universiteit Brussel (VUB)
  • ZorgSaam Hospital
  • Charité - University Medicine Berlin
  • University of Glasgow
  • Shaare Zedek Medical Center
  • Selcuk University
  • National University of Ireland Galway
  • Tiervlei Trial Centre
  • Janssen Pharmaceuticals, US
  • Baylor College of Medicine
  • University of British Columbia
  • University of Toronto
  • McMaster University Medical Centre
  • Karl Bremer Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cardiac and Cardiovascular Systems
Original languageEnglish
Pages (from-to)2191-2201
Number of pages11
JournalNew England Journal of Medicine
Issue number23
Publication statusPublished - 2018 Jun 7
Publication categoryResearch