Reduced‐Dose Versus Full‐Dose Direct Oral Anticoagulants for Extended Secondary Venous Thromboembolism Prophylaxis in Cancer Patients: A Systematic Review and Meta‐Analysis of Randomized Trials

Patients with cancer are at high risk for both recurrent venous thromboembolism (VTE) and anticoagulant‐associated bleeding. Direct oral anticoagulants (DOACs) have become a standard option for long‐term VTE management; however, the safety and efficacy of reduced‐dose regimens in cancer populations remain uncertain. We conducted a systematic review and meta‐analysis of randomized controlled trials (RCTs) comparing reduced‐dose versus full‐dose DOACs in adult patients with active cancer and prior VTE who had completed at least 6 months of therapeutic anticoagulation. Embase and MEDLINE were searched from inception through April 1, 2025. Primary outcomes were recurrent VTE and a composite of major bleeding and clinically relevant non‐major bleeding. Pooled risk ratios (RRs) were calculated using a random‐effects model. Three RCTs including 2178 patients were eligible. There was no significant difference in recurrent VTE between reduced‐dose and full‐dose apixaban or rivaroxaban (RR, 0.87; 95% CI, 0.10–7.83; I 2 = 0%). The composite bleeding risk was numerically lower with reduced‐dose DOACs (RR, 0.77; 95% CI, 0.55–1.06; p = 0.07; I 2 = 0%). In a subgroup analysis of cancer‐only trials (API‐CAT and EVE; n = 2126), reduced‐dose apixaban significantly reduced the risk of clinically relevant bleeding (RR, 0.77; 95% CI, 0.60–0.99; p = 0.05) without increasing VTE recurrence. Reduced‐dose apixaban or rivaroxaban offers comparable efficacy to full‐dose regimens for extended secondary VTE prophylaxis in cancer patients, with a potential reduction in clinically relevant bleeding. These findings support consideration of dose de‐escalation in select patients with active cancer.