Rivaroxaban versus low molecular weight heparin in cancer-associated thrombosis: Assessment of clinical equipoise and bleeding risk from randomized evidence.

e24200 Background: Direct oral anticoagulants are increasingly adopted for cancer-associated thrombosis (CAT) due to ease of administration; however, robust comparative safety and efficacy data against low molecular weight heparin (LMWH) remain limited. We conducted a meta-analysis of randomized trials to evaluate whether rivaroxaban provides superior clinical outcomes in patients with active malignancy. Methods: A systematic search of PubMed, EMBASE, and Cochrane Library identified randomized controlled trials comparing rivaroxaban with LMWH in adults with active cancer and acute venous thromboembolism. Outcomes included recurrent VTE, deep vein thrombosis (DVT), major bleeding, and minor bleeding. Pooled risk ratios (RR) were calculated using random-effects models. Heterogeneity was assessed using I² statistics. Results: Four randomized trials comprising 1,195 patients (rivaroxaban n = 591; LMWH n = 604) were included. Rivaroxaban showed no statistically significant reduction in recurrent VTE compared with LMWH (RR 0.59, 95% CI 0.33–1.05; p = 0.07; I² = 0%) and no difference in DVT recurrence (RR 0.70, 95% CI 0.44–1.12; p = 0.13). Importantly, rivaroxaban demonstrated a numerically higher major bleeding risk (RR 1.47, 95% CI 0.86–2.53) and a significant increase in minor bleeding events (RR 1.90, 95% CI 1.01–3.55; p = 0.05), indicating a clinically relevant bleeding signal. This corresponds to approximately one additional bleeding event for every 53 patients treated with rivaroxaban without a proportional reduction in thrombotic recurrence. Conclusions: In patients with active cancer and venous thromboembolism, rivaroxaban does not provide superior thrombotic protection over LMWH and is associated with increased bleeding events. These findings demonstrate persistent clinical equipoise and suggest that widespread substitution of LMWH with rivaroxaban should be approached cautiously. Personalized anticoagulant selection based on bleeding risk may be critical to optimizing outcomes in this high-risk oncology population.