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

Department

Internal Medicine

Document Type

Article

Publication Title

American Journal of Hematology

Abstract

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; I2 = 0%). The composite bleeding risk was numerically lower with reduced-dose DOACs (RR, 0.77; 95% CI, 0.55-1.06; p = 0.07; I2 = 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.

First Page

2276

Last Page

2285

DOI

10.1002/ajh.70090

Volume

100

Issue

12

Publication Date

12-1-2025

Publisher

Wiley-Liss

Medical Subject Headings

Humans; Venous Thromboembolism; Neoplasms; Randomized Controlled Trials as Topic; Administration, Oral; Hemorrhage; Anticoagulants; Rivaroxaban; Secondary Prevention; Pyridones

PubMed ID

40990099

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