Clinical Question: In patients with acute venous thromboembolism (VTE), is apixaban associated with a lower risk of clinically relevant bleeding than rivaroxaban?
Background: Apixaban and rivaroxaban are the most commonly prescribed oral anticoagulants for acute VTE, recommended as first-line therapy over vitamin K antagonists because of their improved safety profile. In the original trials supporting their use, clinically relevant bleeding occurred in 4.3% of patients on apixaban compared with 9.7% on warfarin, and in 8.1% of patients on rivaroxaban compared with 8.1% on warfarin. Prospective trials directly comparing the two agents have been lacking, and these differing results have been attributed to differences in trial populations and design rather than the drugs themselves. As a result, current guidelines do not recommend one agent over the other, and the choice between them remains at the discretion of the treating clinician.
Study Design: International, prospective, randomized, open-label, blind endpoint (PROBE) trial
Setting: Thirty-two centers in Canada, Australia, and Ireland
Synopsis: A total of 2,760 adults with acute symptomatic venous thromboembolism (proximal deep vein thrombosis [DVT] or pulmonary embolism [PE]) were randomized 1:1 to apixaban (10 mg twice daily for seven days, then 5 mg twice daily) or rivaroxaban (15 mg twice daily for 21 days, then 20 mg daily) for three months. Among the 2,700 patients analyzed, clinically relevant bleeding occurred in 3.3% of the apixaban group versus 7.1% of the rivaroxaban group (relative risk [RR], 0.46; 95% confidence interval [CI], 0.33 to 0.65; P <0.001). Major bleeding alone was also markedly lower with apixaban (0.4% versus 2.4%). Most of the bleeding difference occurred during the first three weeks, when rivaroxaban was given at its higher loading dose. Recurrent VTE was similar between groups (about 1% each), and mortality was low overall. The trial’s open-label design leaves some potential for ascertainment bias. Patients with active cancer, body weight over 120 kg, or creatinine clearance under 30 mL/min were excluded, limiting generalizability to populations commonly seen in hospital medicine.
Bottom Line: Apixaban is associated with significantly lower clinically relevant bleeding compared with rivaroxaban in patients with acute VTE, though current guidelines do not yet favor one agent over the other.
Citation: Castellucci LA, et al. Bleeding risk with apixaban vs. rivaroxaban in acute venous thromboembolism. N Engl J Med. 2026;394(11):1051-1060. doi:10.1056/NEJMoa2510703.
Dr. Choudry
Dr. Choudry is an academic hospitalist and associate division chief of hospital medicine at MedStar Washington Hospital Center and an assistant professor of medicine at Georgetown University School of Medicine, both in Washington, D.C.