Apixaban vs Rivaroxaban: A Clearer Choice for VTE?

Venous thromboembolism (VTE) results from clot formation within the venous circulation and encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE).¹ DVT develops when clots obstruct blood flow in the deep veins, typically those in the legs, whereas PE results when clots embolize in the lungs, leading to partial or complete obstruction of pulmonary circulation. National estimates indicate that VTE leads to approximately 60,000 to 100,000 deaths annually.²

Direct oral anticoagulants, such as apixaban (Eliquis; Bristol Myers Squibb, Pfizer) and rivaroxaban (Xarelto; Johnson & Johnson), are mainstay therapies for patients presenting with DVT or acute symptomatic PE at low risk for complications.^3,4 Although evidence supports the safety of apixaban and rivaroxaban relative to warfarin, researchers had not directly compared their bleeding risk until last year.

In March 2026, the New England Journal of Medicine published findings from COBRRA-AF (NCT04642430),⁵ a randomized open-label trial that assessed the safety of these drugs in acute symptomatic VTE. The study investigators randomly assigned eligible patients to apixaban (n = 1345) or rivaroxaban (n = 1355) for 3 months at doses consistent with prescribing recommendations.⁵ The study reported that 65.7% of patients were adherent to apixaban compared with 75.1% with rivaroxaban. The mean age was 58.3 years; 52.2% of patients had a DVT, and 47.8% had a PE with or without a DVT.

Clinically relevant bleeding, a composite of major bleeding or clinically relevant nonmajor bleeding, occurred in 3.3% of patients receiving apixaban and 7.1% of patients receiving rivaroxaban.⁵ Of these, 5 patients (0.4%) in the apixaban group experienced a major bleeding event causing at least a 2-g/dL decrease in hemoglobin or requiring blood transfusion. In comparison, 32 patients (2.4%) in the rivaroxaban group experienced major bleeding; 28 patients had at least a 2-g/dL hemoglobin decrease or required blood transfusion. For nonmajor bleeding, vaginal and gastrointestinal bleeding occurred in the apixaban group in 2.7% and 0.6% of patients, respectively. In the rivaroxaban group, vaginal bleeding, hematuria, and gastrointestinal bleeding occurred in 3.8%, 1.3%, and 1.0% of patients, respectively. Bleeding occurred more often with rivaroxaban than apixaban during the first 21 days of therapy, suggesting that the rivaroxaban loading dose may increase bleeding risk.⁵

With respect to efficacy outcomes, VTE recurred in 15 patients (1.1%) receiving apixaban and 14 patients (1.0%) receiving rivaroxaban.⁵ Death from any cause was unrelated to VTE recurrence and occurred in 1 patient in the apixaban group and 4 patients in the rivaroxaban group. Although efficacy is comparable, apixaban offers a more favorable safety profile than rivaroxaban.⁵

Implications by Practice Area

Pharmacists are in a key position to optimize anticoagulant selection for VTE by incorporating bleeding risk into decision-making when choosing between apixaban and rivaroxaban. They can educate the health care team about the increased risk of early bleeding with rivaroxaban, especially during the first 21 days of treatment.

Regardless of therapy, pharmacists can reinforce the importance of adherence to therapy.

REFERENCES

1. About venous thromboembolism (blood clots). CDC. March 5, 2025. Accessed June 10, 2026. https://www.cdc.gov/blood-clots/about/index.html

2. Data and statistics on venous thromboembolism. CDC. January 27, 2025. Accessed June 10, 2026. https://www.cdc.gov/blood-clots/data-research/facts-stats/index.html

3. Writing Committee Members; Creager MA, Barnes GD, Giri J, et al. 2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN guideline for the evaluation and management of acute pulmonary embolism in adults: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2026;153(12):e977-e1051. doi:10.1161/CIR.0000000000001415

4. Malgor RD, Etkin Y, Mouawad NJ, et al. The American Venous Forum clinical practice guideline on the care of patients with upper extremity deep venous thrombosis. J Vasc Surg Venous Lymphat Disord. 2026;14(4):102461. doi:10.1016/j.jvsv.2026.102461

5. 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