The Efficacy of Different Treatment Strategies of Direct Oral Anticoagulants in Cancer-Associated Thrombosis: A Systematic Review and Network Meta-Analysis

Introduction: CAT is a significant cause of morbidity and mortality among cancer patients. Although DOACs are increasingly utilized, the optimal regimen and treatment duration remain uncertain. This systematic review and network meta-analysis (NMA) aimed to compare the efficacy and safety of various DOAC strategies in managing CAT. Methods: A comprehensive search of PubMed, Embase, the Cochrane Library, and Web of Science was conducted up to March 2025 to identify randomized controlled trials (RCTs) involving adult patients with active cancer and confirmed venous thromboembolism (VTE). A frequentist random-effects NMA framework was employed to evaluate outcomes related to recurrent VTE, major bleeding, and all-cause mortality. Results: Fifteen RCTs involving 8,468 patients were included. Reduced-dosage long-term DOAC therapy significantly decreased the risk of thrombosis recurrence compared to VKAs (odds ratio OR: 0.32, 95% confidence interval CI: 0.11–0.92) and dalteparin (OR: 0.33, 95% CI: 0.13–0.88). Dalteparin exhibited the lowest risk of major bleeding compared to VKAs (OR: 0.49, 95% CI: 0.25–0.97). No significant differences in all-cause mortality were observed among the treatment strategies. Subgroup analysis indicated that 18 months of DOAC therapy provided superior thrombosis prevention compared to 6 months (OR: 0.26, 95% CI: 0.10–0.68). The certainty of evidence was rated as moderate across outcomes. Conclusion: Reduced-dosage long-term DOAC therapy appears to offer a favorable balance between efficacy and safety for managing CAT, while dalteparin remains preferable for patients at high bleeding risk. Extended-duration DOAC therapy may further enhance thrombosis prevention in selected patient populations. Further high-quality head-to-head trials are warranted.