Efficacy and safety of reduced-dose versus full-dose DOACs in extended treatment of VTE: A systematic review and meta-analysis.

Abstract

Extended anticoagulation is recommended for venous thromboembolism (VTE) patients at high recurrence risk. However, the optimal long-term dosing strategy for direct oral anticoagulants (DOACs) remains uncertain. This meta-analysis compares the efficacy and safety of reduced-dose versus full-dose DOACs during extended-phase VTE treatment. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing reduced-dose (apixaban 2.5 mg BID or rivaroxaban 10 mg QD) and full-dose (apixaban 5 mg BID or rivaroxaban 20 mg QD) DOACs. Searches were performed in PubMed, Cochrane CENTRAL, Embase and Scopus till June 10, 2025. Outcomes included recurrent VTE, major bleeding, clinically relevant non-major bleeding (CRNMB), and all-cause mortality. Risk ratios (RRs) were pooled using random-effects models. Five RCTs comprising 8,781 patients were analyzed. Reduced-dose DOACs significantly lowered major bleeding risk (RR: 0.62; 95% CI: 0.42-0.92; p = 0.02; I² = 12%) and CRNMB (RR: 0.75; 95% CI: 0.63-0.88; p = 0.0006; I² = 0%) compared to full-dose DOACs. No significant differences were observed between the groups in recurrent VTE (RR: 0.94; 95% CI: 0.68-1.29; p = 0.70; I² = 0%) or all-cause mortality (RR: 0.86; 95% CI: 0.63-1.17; p = 0.35; I² = 42%). No significant differences across outcomes were observed between cancer-associated and general VTE populations. Reduced-dose DOACs significantly lower bleeding risk without compromising efficacy in preventing recurrent VTE. These findings support the preferential use of reduced-dose DOACs as a safer and effective option for extended anticoagulation, especially in patients at elevated bleeding risk.