Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease

John Eikelboom , Stuart Connolly , Jackie Bosch , Gilles Dagenais , Robert Hart , Olga Shestakovska , Rafael Díaz , Marco Alings , Eva Lonn , Sonia Anand , Petr Widimsky , Masatsugu Hori , Alvaro Avezum , Leopoldo Piegas , Kelley Branch , Jeffrey Probstfield , Deepak Bhatt , Jun Zhu , Yan Liang , Aldo Maggioni , Patricio Lopez-Jaramillo , Martin O'Donnell , Ajay Kakkar , Keith Fox , Alexander Parkhomenko , Georg Ertl , Stefan Störk , Matyas Keltai , Lars Ryden , Nana Pogosova , Antonio Dans , Fernando Lanas , Patrick Commerford , Christian Torp-Pedersen , Tomek Guzik , Peter Verhamme , Dragos Vinereanu , Jae-Hyung Kim , Andrew Tonkin , Basil Lewis , Camilo Felix , Khalid Yusoff , P Gabriel Steg (1, 2) , Kaj Metsarinne , Nancy Cook Bruns , Frank Misselwitz , Edmond Chen , Darryl Leong , Salim Yusuf , Compass Investigators

1 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
2 UPD7 - Université Paris Diderot - Paris 7

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=-4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).

Domaines: Médecine humaine et pathologie

John Eikelboom, Stuart Connolly, Jackie Bosch, Gilles Dagenais, Robert Hart, et al.. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. New England Journal of Medicine, 2017, 377 (14), pp.1319 - 1330. ⟨10.1056/NEJMoa1709118⟩. ⟨hal-01892329⟩