Apixaban causes less bleeding than rivaroxaban
In acute symptomatic blood clots in the legs or lungs, apixaban caused fewer clinically important bleeding events than rivaroxaban over 3 months.
*Randomized trial with blinded outcome review; Level 1b (OCEBM).
Citation
Castellucci LA, Chen VM, Kovacs MJ, et al.; COBRRA Trial Investigators. Bleeding Risk with Apixaban vs. Rivaroxaban in Acute Venous Thromboembolism. N Engl J Med. 2026;394(11):1051-1060. doi:10.1056/NEJMoa2510703.
Background
Apixaban and rivaroxaban are widely used to treat new blood clots in veins, but it has been unclear which has a lower bleeding risk when compared directly.
Patients
Adults (≥18 years) with symptomatic acute pulmonary embolism (segmental or more proximal) or proximal deep-vein thrombosis. Excluded: severe kidney impairment (estimated filtration <30 ml/min), active cancer, weight >120 kg, pregnancy/breastfeeding, active bleeding, or another need for long-term blood thinners (e.g., irregular heartbeat).
Intervention
Apixaban: 10 mg twice daily for 7 days, then 5 mg twice daily.
Control
Rivaroxaban: 15 mg twice daily for 21 days, then 20 mg daily.
Outcome
(Primary) Clinically relevant bleeding (major or clinically important nonmajor bleeding). Secondary outcomes included death from any cause and recurrent blood clots.
Follow-up Period
3 months.
Results
| Outcome |
Apixaban |
Rivaroxaban |
Relative risk (95% CI) |
Absolute risk reduction |
NNT |
| Clinically relevant bleeding (primary) |
3.3% (44/1345) |
7.1% (96/1355) |
0.46 (0.33–0.65) |
3.8% |
27 |
| Major bleeding |
0.4% (5/1345) |
2.4% (32/1355) |
0.16 (0.06–0.40) |
2.0% |
50 |
| Clinically important nonmajor bleeding |
2.9% (39/1345) |
4.9% (67/1355) |
0.59 (0.40–0.86) |
2.0% |
50 |
Primary outcome analysis was intention-to-treat (patients who completed follow-up), by assigned group.
Limitations
Patients and clinicians were not blinded, which may affect reporting. Follow-up was only 3 months. Several groups were excluded (cancer, weight >120 kg, severe kidney disease), and racial/ethnic diversity was limited. The study was not powered to detect differences in recurrent blood clots; apixaban adherence was lower.
Funding
Canadian Institutes of Health Research and other public/nonprofit funders; no funder role.
Clinical Application
For most eligible patients with new leg or lung clots needing 3 months of treatment, prefer apixaban over rivaroxaban to reduce bleeding risk.