Safety and Efficacy of Direct Oral Anticoagulants Versus Standard Therapy for Venous Thromboembolism in Cancer Patients: A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials

Background: Patients with malignancy demonstrate an elevated risk of developing venous thromboembolism (VTE) due to coagulopathy and treatment modalities. Although low-molecular-weight heparin (LMWH) and warfarin have historically been standard therapies, direct oral anticoagulants (DOACs) are increasingly used in this population. Methods: We conducted a Bayesian network meta-analysis to compare the safety and efficacy of apixaban, edoxaban, rivaroxaban, LMWH, and warfarin in cancer-associated VTE. A comprehensive literature search of Embase, Medline, clinical trial registries, and manual sources was performed up to November 2025. The primary outcome was to compare the risk of VTE recurrence across therapies. Secondary outcomes included major bleeding, clinically relevant non-major bleeding (CRNMB), and all-cause mortality. Odds ratios (ORs) with 95% credible intervals (CrIs) were estimated, and treatment rankings were derived using the surface under the cumulative ranking curves (SUCRA) probabilities. Results: Seven randomized controlled trials (RCTs) involving 3325 patients were included. No clear evidence of differences was observed among apixaban, rivaroxaban, edoxaban, low-molecular-weight heparin, and warfarin for VTE recurrence, major bleeding, clinically relevant non-major bleeding, and mortality. For instance, rivaroxaban showed no statistically significant difference in VTE recurrence compared with apixaban (OR 1.13; 95% CrI 0.17–12.27), warfarin (OR 0.60; 95% CrI 0.03–19.00), edoxaban (OR 0.77; 95% CrI 0.06–11.11), or LMWH (OR 0.51; 95% CrI 0.10–2.66). Wide credible intervals reflect uncertainty due to the limited number of RCTs and low event rates. Conclusions: This Bayesian network meta-analysis showed no statistically significant differences between therapies with respect to VTE recurrence, bleeding outcomes, and mortality. However, the wide credible intervals indicate limited precision, warranting cautious interpretation of the findings.