Rivaroxaban for secondary stroke prevention after embolic stroke of undetermined source

Hart, R. G. et al. (2018) Rivaroxaban for secondary stroke prevention after embolic stroke of undetermined source. New England Journal of Medicine, 378(23), pp. 2191-2201. (doi: 10.1056/NEJMoa1802686) (PMID:29766772)

Abstract

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. (Funded by Bayer and Janssen Research and Development; NAVIGATE ESUS ClinicalTrials.gov number, NCT02313909.)

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Muir, Professor Keith
• Authors: Hart, R. G., Sharma, M., Mundl, H., Kasner, S. E., Bangdiwala, S. I., Berkowitz, S. D., Swaminathan, B., Lavados, P., Wang, Y., Wang, Y., Davalos, A., Shamalov, N., Mikulik, R., Cunha, L., Lindgren, A., Arauz, A., Lang, W., Czlonkowska, A., Eckstein, J., Gagliardi, R. J., Amarenco, P., Ameriso, S. F., Tatlisumak, T. T., Veltkamp, R., Hankey, G. J., Toni, D., Bereczki, D., Uchiyama, S., Ntaios, G., Yoon, B.-W., Brouns, R., Endres, M., Muir, K. W., Bornstein, N., Ozturk, S., O’Donnell, M. J., De Vries Basson, M. M., Pare, G., Pater, C., Kirsch, B., Sheridan, P., Peters, G., Weitz, J. I., Peacock, W. F., Shoamanesh, A., Benavente, O. R., Joyner, C., Themeles, E., and Connolly, S. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: New England Journal of Medicine
• Publisher: Massachusetts Medical Society
• ISSN: 0028-4793
• ISSN (Online): 1533-4406
• Published Online: 16 May 2018
• Copyright Holders: Copyright © 2018 Massachusetts Medical Society
• First Published: First published in New England Journal of Medicine 378(23): 2191-2201
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher