Efficacy and safety of low-dose versus standard-dose direct oral anticoagulants for secondary prevention of cancer-associated thrombosis: a systematic review and meta-analysis

BACKGROUND: Cancer-associated thrombosis is a major cause of morbidity and mortality in patients with cancer and is associated with a high risk of both recurrent venous thromboembolism (VTE) and bleeding. Although extended anticoagulation reduces the risk of recurrent VTE by more than 80%, full-dose therapy may increase bleeding complications, potentially offsetting its benefit in this population. Reduced-dose direct oral anticoagulants (DOACs) have therefore been proposed as a safer long-term treatment option. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials comparing reduced-dose DOACs with standard-dose regimens for extended VTE treatment in cancer patients. Outcomes included recurrent VTE, major bleeding, clinically relevant nonmajor bleeding, all-cause mortality, and composite bleeding, with pooled odds ratios calculated using random-effects models. RESULTS: Five randomized trials involving 2709 patients were included. Recurrent VTE rates were comparable between reduced-dose and standard-dose DOACs. Reduced-dose therapy was associated with a significant reduction in clinically relevant nonmajor bleeding and composite bleeding. While major bleeding occurred less, the difference was not statistically significant. CONCLUSIONS: Overall, reduced-dose DOACs demonstrated similar efficacy in preventing recurrent VTE while offering an improved bleeding profile, supporting their potential role in long-term management of cancer-associated thrombosis, though larger prospective studies are needed to define optimal dosing strategies.