Reduced-Dose Versus Full-Dose Direct Oral Anticoagulants for Extended Treatment of Venous Thromboembolism: A Meta-Analysis of Randomized Controlled Trials

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. 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. 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. 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. 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.