Effectiveness and Safety of Apixaban Versus Warfarin in Atrial Fibrillation Patients with Malignancy: A Propensity-Matched Analysis

Patients with atrial fibrillation and malignancy have increased risks of thromboembolism and bleeding. Evidence comparing apixaban and warfarin in this group remains limited. We aimed to compare effectiveness and safety of apixaban versus warfarin in patients with atrial fibrillation and active malignancy using real-world data from a large multinational cohort. This retrospective cohort study used the TriNetX Global Collaborative Network, de-identified records from 146 healthcare organizations between December 1, 2012, and May 1, 2025. Atrial fibrillation patients with malignancy receiving apixaban or warfarin 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. In this 12.5-year period, 41,764 matched pairs of patients were analyzed. Compared to the warfarin cohort, the apixaban cohort demonstrated 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). Stroke rates were comparable between groups, while pulmonary embolism, deep vein thrombosis, gastrointestinal bleeding and intracranial hemorrhage were noted less frequent with apixaban. Kaplan-Meier analyses showed early and sustained differences in survival and bleeding outcomes. In conclusion, in atrial fibrillation patients with cancer, apixaban was associated with lower mortality and major bleeding without increasing stroke risk compared to warfarin.