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.
