Comparing survival with vitamin K antagonists, low-molecular-weight heparin, and direct oral anticoagulants in patients with cancer-a systematic review and meta-analysis.

Background: Venous thromboembolism (VTE) is a frequent complication in malignancy. Low-molecular-weight heparins and direct oral anticoagulants have replaced vitamin K antagonists (VKAs) as the standard of care for cancer-associated VTE. Nonetheless, clinical trials have not established a survival benefit of these agents compared with VKA. Objectives: We conducted a systematic review and meta-analysis to compare survival in cancer patients receiving VKA vs other anticoagulants. Methods: We searched Embase, Web of Science, PubMed, ClinicalTrials.gov, and Cochrane from inception until April 10, 2025, focusing on the use of VKA and non-VKA in cancer patients. Primary outcome was mortality and secondary outcomes included thromboembolism and bleeding. Results: Of 11,198 studies screened, 14 studies (70,025 patients) were included. VKA were associated with lower mortality than non-VKA in observational studies (odds ratio [OR], 0.84; 95% CI, 0.78-0.91; I 2 = 81%; n = 6 studies) but not in randomized controlled trials (OR, 0.99; 95% CI, 0.86-1.13; I 2 = 0%; n = 8 studies). In subgroup analysis, follow-up period of >6 months (OR, 0.85; 95% CI, 0.79-0.92; I 2 = 75%), solid malignancies (OR, 0.81; 95% CI, 0.75-0.88; I 2 = 78%), and indication of VTE only (OR, 0.89; 95% CI, 0.83-0.96; I 2 = 42%) demonstrated improved survival with VKA. Conclusion: The use of VKA was associated with lower mortality than non-VKA anticoagulation in patients with cancer in observational studies but not in randomized trials. The analysis was limited by high heterogeneity, which must be considered when interpreting results.