TY - JOUR
T1 - Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease
AU - Eikelboom, John W
AU - Connolly, Stuart J
AU - Bosch, Jackie
AU - Dagenais, Gilles R
AU - Hart, Robert G
AU - Shestakovska, Olga
AU - Diaz, Rafael
AU - Alings, Marco
AU - Lonn, Eva M
AU - Anand, Sonia S
AU - Widimsky, Petr
AU - Hori, Masatsugu
AU - Avezum, Alvaro
AU - Piegas, Leopoldo S
AU - Branch, Kelley R H
AU - Probstfield, Jeffrey
AU - Bhatt, Deepak L
AU - Zhu, Jun
AU - Liang, Yan
AU - Maggioni, Aldo P
AU - Lopez-Jaramillo, Patricio
AU - O'Donnell, Martin
AU - Kakkar, Ajay K
AU - Fox, Keith A A
AU - Parkhomenko, Alexander N
AU - Ertl, Georg
AU - Störk, Stefan
AU - Keltai, Matyas
AU - Ryden, Lars
AU - Pogosova, Nana
AU - Dans, Antonio L
AU - Lanas, Fernando
AU - Commerford, Patrick J
AU - Torp-Pedersen, Christian
AU - Guzik, Tomek J
AU - Verhamme, Peter B
AU - Vinereanu, Dragos
AU - Kim, Jae-Hyung
AU - Tonkin, Andrew M
AU - Lewis, Basil S
AU - Felix, Camilo
AU - Yusoff, Khalid
AU - Steg, P Gabriel
AU - Metsarinne, Kaj P
AU - Cook Bruns, Nancy
AU - Misselwitz, Frank
AU - Chen, Edmond
AU - Leong, Darryl
AU - Yusuf, Salim
N1 - Publisher Copyright:
Copyright © 2017 Massachusetts Medical Society.
PY - 2017/10/5
Y1 - 2017/10/5
N2 - 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.
AB - 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.
KW - Aged
KW - Aspirin/adverse effects
KW - Atherosclerosis/complications
KW - Cardiovascular Diseases/drug therapy
KW - Double-Blind Method
KW - Drug Therapy, Combination
KW - Factor Xa Inhibitors/adverse effects
KW - Female
KW - Hemorrhage/chemically induced
KW - Humans
KW - Male
KW - Middle Aged
KW - Platelet Aggregation Inhibitors/adverse effects
KW - Rivaroxaban/adverse effects
KW - Secondary Prevention/methods
U2 - 10.1056/NEJMoa1709118
DO - 10.1056/NEJMoa1709118
M3 - Article
C2 - 28844192
SN - 0028-4793
VL - 377
SP - 1319
EP - 1330
JO - The New England journal of medicine
JF - The New England journal of medicine
IS - 14
ER -