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Safety and Effectiveness of Direct Oral Anticoagulants Versus Low-Molecular-Weight Heparin for Cancer-Associated Thrombosis: A Systematic Review and Meta-analysis.

Wei Kang·Bowie P Y Lam·Rinko Tsz Lam Lau·Silvia T H Li·Kangrui Wu·Yue Wei·Yu Yang·Kyung Jin Lee·Caige Huang·Vincent K C Yan·Hei Hang Edmund Yiu·Shing Fung Lee·Aya El Helali·Victor H F Lee·Stephen L Chan·Rina Y M Hui·Ka On Lam·Esther W Chan
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Abstract

BACKGROUND: Cancer-associated thrombosis is a condition associated with high mortality rates, yet limited evidence exists regarding the safety and effectiveness of low-molecular-weight heparin (LMWH) and direct oral anticoagulants (DOACs), focusing on a fixed follow-up period based on clinical practice guideline recommendations. OBJECTIVE: This study aimed to compare the safety and effectiveness of DOACs versus LMWH in patients with cancer-associated thrombosis over a 6-month follow-up period. METHODS: PubMed, Embase, and Cochrane Library databases were systematically searched up to 30 June, 2025. Recurrent venous thromboembolism, major bleeding, and all-cause mortality were pooled using a random-effects meta-analysis. RESULTS: Seven randomized controlled trials and 28 cohort studies were included in our systematic review. After applying the criteria for a 6-month follow-up period, five randomized controlled trials and 16 cohort studies with 49,824 patients were analyzed in the meta-analysis. In randomized controlled trials, DOACs showed a lower incidence of venous thromboembolism recurrence (relative risk [RR] 0.66, 95% confidence interval [CI] 0.49-0.87) compared with LMWH, with a non-significant increase in major bleeding (RR 1.28, 95% CI 0.87-1.88) and no significant difference in all-cause mortality (RR 1.00, 95% CI 0.86-1.18). Cohort studies demonstrated a lower incidence of venous thromboembolism recurrence (RR 0.69, 95% CI 0.62-0.76) with DOACs, a non-significant reduction in major bleeding (RR 0.85, 95% CI 0.68-1.07), and a lower risk of all-cause mortality (RR 0.47, 95% CI 0.31-0.72). CONCLUSIONS: In patients with cancer-associated thrombosis, DOACs demonstrated a decrease in recurrent venous thromboembolism without increasing the risk of all-cause mortality. A non-significant increase in the risk of major bleeding was recorded in randomized controlled trials, but not in cohort studies. DOACs may provide greater effectiveness for cancer-associated thrombosis compared with LMWH.

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HumansHeparin, Low-Molecular-WeightNeoplasmsAnticoagulantsHemorrhageThrombosisAdministration, OralRandomized Controlled Trials as TopicVenous ThromboembolismJournal ArticleSystematic ReviewMeta-AnalysisComparative Study

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Wei Kang, Bowie P Y Lam, Rinko Tsz Lam Lau, Silvia T H Li, Kangrui Wu, Yue Wei, Yu Yang, Kyung Jin Lee, Caige Huang, Vincent K C Yan, Hei Hang Edmund Yiu, Shing Fung Lee, Aya El Helali, Victor H F Lee, Stephen L Chan, Rina Y M Hui, Ka On Lam, Esther W Chan. 2026-06-15. Safety and Effectiveness of Direct Oral Anticoagulants Versus Low-Molecular-Weight Heparin for Cancer-Associated Thrombosis: A Systematic Review and Meta-analysis.. https://doi.org/10.1007/s40264-026-01684-4

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