Reduced-dose vs full-dose direct oral anticoagulants for extended treatment of venous thromboembolism: a meta-analysis of randomized controlled trials.

BACKGROUND: Venous thromboembolism (VTE) is a major cause of cardiovascular morbidity and mortality globally. Although direct oral anticoagulants (DOACs) have improved extended VTE treatment, the optimal dose for balancing efficacy and safety remains unclear. OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of reduced-dose DOACs vs full-dose regimens during extended anticoagulation for VTE. METHODS: A literature search of PubMed, Embase, and Cochrane Library was performed up to April 2025 to identify randomized controlled trials (RCTs) comparing reduced-dose vs full-dose DOACs for extended VTE treatment in patients with or without cancer. Risk ratios (RR) and 95% CIs were estimated using a random-effects model. Primary outcomes were recurrent VTE and major or clinically relevant nonmajor bleeding. The secondary outcomes included major bleeding, clinically relevant nonmajor bleeding, all-cause mortality, and VTE-related mortality. RESULTS: Five RCTs involving 8781 patients were included in the meta-analysis. The mean ± SD age of patients was 61.3 ± 13.4 years, and median follow-up duration was 12 months. Reduced-dose DOACs were comparable with full-dose regimens in preventing recurrent VTE (RR, 0.94; 95% CI, 0.68-1.29) and all-cause death (RR, 0.86; 95% CI, 0.63-1.17). However, reduced-dose DOACs significantly lowered the risk of major or clinically relevant nonmajor bleeding (RR, 0.71; 95% CI, 0.61-0.82), major bleeding (RR, 0.62; 95% CI, 0.42-0.92), and clinically relevant nonmajor bleeding (RR, 0.75; 95% CI, 0.63-0.88) compared with full-dose regimens. No significant subgroup differences were observed between cancer-associated and general VTE populations. CONCLUSION: Reduced-dose DOACs are as effective as full-dose regimens in preventing recurrent VTE and are associated with significantly lower bleeding risks. However, more RCTs with extended follow-up and focused inclusion of cancer patients are warranted to validate these findings.

Duke Scholars

Author Stephen Greene Medicine, Cardiology

Author Robert John Mentz Medicine, Cardiology

Author Marat Fudim Medicine, Cardiology