DOACs versus vitamin K antagonists for cancer-associated VTE: Updated systematic review and meta-analysis.

e23324 Background: Cancer-associated venous thromboembolism (VTE) remains a major driver of morbidity and mortality, and anticoagulant choice requires balancing recurrence prevention against bleeding risk. While low–molecular–weight heparin has historically been preferred, direct oral anticoagulants (DOACs) are increasingly used in routine practice, including in patients underrepresented in randomized trials (older age, mixed malignancy types, variable treatment status, and comorbidity burden). Therefore, we performed an updated systematic review and meta-analysis to clarify the effectiveness and safety of DOACs versus VKAs in adults with active cancer and VTE across contemporary clinical settings. Methods: We synthesized 10 comparative observational studies (retrospective cohorts and database-based analyses) enrolling adults (≥18 years) with active solid or hematologic malignancy and objectively confirmed VTE (deep vein thrombosis and/or pulmonary embolism) treated with DOACs (apixaban, rivaroxaban, edoxaban, dabigatran) or VKAs (warfarin/other VKAs with INR-guided dosing, with or without initial parenteral anticoagulation). Primary outcomes were recurrent VTE and major bleeding; secondary outcomes included all-cause mortality. Random-effects models pooled adjusted hazard ratios (HRs) for time-to-event outcomes and risk ratios (RRs) were reported. Heterogeneity was assessed using I², with leave-one-out sensitivity analyses. Results: Across 49,806 patients (DOACs: 22,817; VKAs: 26,989), DOACs were associated with lower adjusted recurrent VTE (HR 0.73, 95% CI 0.68–0.79; I² = 0.0%; prediction interval 0.59–0.91) and lower unadjusted recurrent VTE (RR 0.72, 95% CI 0.62–0.83; I² = 13.7%; prediction interval 0.59–0.87). DOACs also reduced adjusted major bleeding (HR 0.83, 95% CI 0.72–0.97; I² = 0.0%), though statistical significance was sensitive to omission of one large study. Adjusted all-cause mortality was lower with DOACs (RR 0.46, 95% CI 0.36–0.60; I² = 0.0%), but prediction intervals were wide, and results were influenced by individual studies. No clear funnel-plot asymmetry was observed. Conclusions: In adults with active cancer and VTE treated in real-world settings, DOACs were associated with reduced recurrent VTE and lower major bleeding compared with VKAs, with low heterogeneity across studies. Mortality estimates should be interpreted cautiously due to observational design and imprecision. Prospective comparative studies are needed to confirm survival effects and optimize anticoagulant selection in heterogeneous oncology populations.