CLINICAL QUESTION: How do the three most prescribed oral anticoagulants compare in regard to venous thromboembolism (VTE) recurrence, prevention, and major bleeding?
BACKGROUND: Oral anticoagulants substantially reduce the risk of recurrent VTE. Since 2012, direct-acting oral anticoagulants (DOACs) have increasingly replaced warfarin, and in 2021, the American College of Chest Physicians recommended DOACs over warfarin for most patients with VTE. However, guidelines do not distinguish between DOACs, and head-to-head data remains limited.
STUDY DESIGN: Retrospective, population-based, cohort study
SETTING: Three U.S. administrative healthcare databases, including both publicly and commercially insured patients from 2016 to 2024
SYNOPSIS: A total of 163,593 adults from three U.S. claims databases (2016 to 2024) who initiated apixaban, rivaroxaban, or warfarin within 30 days of VTE discharge were analyzed. Eligible patients were 18 years old or older, with at least 365 days of continuous insurance coverage. Exclusions included prior DOAC use, VTE hospitalization within the past year, end-stage kidney disease, or palliative care. Propensity score-matching weights adjusted for confounding. The mean age was 71.4 years; 56.7% were female. Treatment distribution was 58.5% apixaban, 25.7% rivaroxaban, and 15.8% warfarin.
Weighted incidence rates (per 1,000 person-years) for recurrent VTE were 23.3 (apixaban), 26.8 (rivaroxaban), and 38.3 (warfarin). Major bleeding rates were 30.6, 44.6, and 47.2, respectively. Apixaban was associated with lower recurrent VTE than rivaroxaban (HR, 0.87; 95% CI, 0.78 to 0.96) and warfarin (HR, 0.77; 95% CI, 0.69 to 0.87), and lower major bleeding than rivaroxaban (HR, 0.69; 95% CI, 0.63 to 0.75) and warfarin (HR, 0.70; 95% CI, 0.64 to 0.76). All-cause mortality was similar across agents. In patients with active cancer, DOACs were associated with higher mortality than warfarin, a finding that may reflect limitations of the study’s observational design and reliance on administrative claims.
BOTTOM LINE: Apixaban demonstrated the best balance of safety and efficacy with lower rates of recurrent VTE and major bleeding when compared to rivaroxaban and warfarin, with comparable all-cause mortality.
CITATION: Bea S, et al. Oral anticoagulation and risk of adverse clinical outcomes in venous thromboembolism. JAMA Intern Med. 2025;185(7):837-846. doi: 10.1001/jamainternmed.2025.1109.
Dr. Snyder
Dr. Snyder is a hospitalist at the Nebraska Medical Center and an assistant professor in the department of internal medicine at the University of Nebraska Medical Center, both in Omaha, Neb.