Evidence comparing direct oral anticoagulants and warfarin in patients with atrial fibrillation (AF) and cancer remains limited. This retrospective cohort study, published in the American Journal of Cardiology, used the TriNetX Global Collaborative Network, comprising de-identified records from 146 healthcare organizations between December 1, 2012, and May 1, 2025. Adults with AF and malignancy receiving apixaban or warfarin were identified. Patients were matched 1:1 using propensity scores across 74 clinical variables. Outcomes were assessed at 3 months, 6 months, 1 year, and 5 years. Primary endpoints included all-cause mortality, stroke, pulmonary embolism, deep vein thrombosis, gastrointestinal bleeding, and intracranial hemorrhage.

During the 12.5-year study period, 41,764 matched pairs were analyzed. In propensity-matched analyses, apixaban use was associated with lower all-cause mortality at 3 months (OR 1.05, 95% CI 1.00–1.10), 6 months (OR 1.05, 95% CI 1.01–1.09), 1 year (OR 1.06, 95% CI 1.03–1.10), and 5 years (OR 1.17, 95% CI 1.13–1.20; all P<0.05) compared with warfarin. Stroke rates were comparable between groups. Pulmonary embolism, deep vein thrombosis, gastrointestinal bleeding, and intracranial hemorrhage were less frequent in the apixaban cohort. Kaplan–Meier analyses showed early and sustained differences in survival and bleeding outcomes.

In this multinational propensity-matched cohort, apixaban was associated with lower mortality and major bleeding without increased stroke risk compared with warfarin.