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Patient Evidence Summary
Doctor, I was just diagnosed with a blood clot and need to start a blood thinner. Between apixaban (Eliquis) and rivaroxaban (Xarelto), which causes less bleeding?
In this study, people who had a new blood clot in the extremities (deep vein thrombosis, DVT) or in their lungs (pulmonary embolism, PE) had a lower risk of bleeding when treated with apixaban than with rivaroxaban during the first 3months of treatment. This included bleeding that required medical attention.
Study highlights
Out of 100 people treated for a new blood clot, about four fewer people had bleeding that required medical attention with apixaban than rivaroxaban. The risk of having a new symptomatic blood clot did not clearly differ between the two medications.
Understanding the problem
A venous thromboembolism (VTE) is a blood clot in the lungs (pulmonary embolism, PE) or the legs (deep vein thrombosis, DVT). People diagnosed with VTE are usually treated with blood thinners. Apixaban and Rivaroxaban are both commonly prescribed medications from a class of blood thinners called direct oral anticoagulants, which are preferred to older medications in that they do not require frequent monitoring or injections.
While all blood thinners carry a risk of bleeding, it was not known whether apixaban or rivaroxaban had a lower bleeding risk when used to treat a new blood clot.
The COBRRA study included a total of 2760 adult patients who were newly diagnosed with a DVT or PE and had normal kidney function. Participants were randomly assigned to receive either apixaban or rivaroxaban treatment for 3 months. Patients who didn’t have any symptoms from their blood clots, were on blood thinners for other reasons, had cancer, significant liver disease, or were greater than 120 kg were not included in this study.
The main outcome was clinically relevant bleeding, meaning major bleeding or other bleeding that required medical attention. The study also looked at recurrence of the blood clot, death, and adherence to the medication. Patients were followed for 3 months after starting treatment.
Apixaban vs Rivaroxaban for the treatment of VTE
Outcome | Apixaban | Rivaroxaban | Results |
|---|---|---|---|
Clinically relevant bleeding* | 3 in a 100 people | 7 in a 100 people | About 4 fewer in a 100 people had clinically relevant bleeding on apixaban compared to rivaroxaban |
Recurrent symptomatic blood clot | 1 in a 100 people | 1 in a 100 people | No clear difference between groups |
| Death from any cause | 1 in a 1000 people | 3 in a 1000 people | No clear difference between groups** |
*Clinically relevant bleeding is any bleeding that required patients to seek medical attention
**Although the rates for the 2 groups look different, the differences were not statistically significant—this means that the difference could simply be due to chance rather than due to the different treatments.
In summary, the COBRRA study found that apixaban caused less clinically relevant bleeding than rivaroxaban during the first 3 months of treatment for a new VTE. The study did not show a clear difference between the 2 medications in recurrent symptomatic blood clots.
This Evidence Summary is based on the following article:
Castellucci LA, Chen VM, Kovacs MJ, et al. Bleeding Risk with Apixaban vs. Rivaroxaban in Acute Venous Thromboembolism. N Engl J Med. 2026 Mar 12;394(11):1051-1060. doi: 10.1056/NEJMoa2510703. PubMed
Darsh Shah, MD
Darsh Shah is a second year Internal Medicine resident at McMaster University where he also completed his medical training. His clinical interests include Hematology/Thrombosis and he has a research interest in Medical Education.
Anthony Sandre, MD
Dr. Sandre is an Assistant Professor in the Division of General Internal Medicine at McMaster University with additional training in Vascular Medicine. Within the Division of Hematology and Thromboembolism, Dr. Sandre provides care to patients with arterial and venous thrombosis, arteriopathies, and high-risk primary or secondary prevention of cardiovascular disease.
Published: Monday, July 13, 2026
Please note that the information contained herein is not to be interpreted as an alternative to medical advice from a professional healthcare provider. If you have any questions about any medical matter, you should consult your professional healthcare providers, and should never delay seeking medical advice, disregard medical advice or discontinue medication based on information provided here.
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This Evidence Summary was printed from the CLOT+ website on 2026/07/15. To view other Evidence Summaries or to register to receive email notifications about new Evidence Summaries, please visit us at https://plus.mcmaster.ca/ClotPlus/Articles/EvidenceSummaries |
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, McMaster University