Reduced-Dose Versus Full-Dose Direct Oral Anticoagulants in the Extended Treatment of Venous Thromboembolism: A Systematic Review and Meta-Analysis.

Purpose: The optimal dosing strategy for direct oral anticoagulants (DOACs) in extended treatment of venous thromboembolism (VTE) remains debated, particularly in balancing efficacy and bleeding risk.

Methods: A systematic review and meta-analysis was performed to compare reduced-dose versus full-dose DOACs for extended VTE treatment. Databases including PubMed, Embase, and Cochrane Library were searched from inception to March 2025 for randomized controlled trials (RCTs) involving adult patients treated with different DOAC doses for VTE. Primary outcomes were recurrent VTE, major or clinically relevant non-major bleeding, and all-cause mortality. Subgroup analysis was conducted by DOAC type (apixaban vs. rivaroxaban).

Results: Pooled data from 4 studies involving 8421 patients showed no statistically significant difference in recurrent VTE risk between reduced-dose and full-dose DOACs (RR = 0.94; 95% CI, 0.64-1.37; p = 0.75). Bleeding events were significantly lower in the reduced-dose group compared to the full-dose group (RR = 0.71; 95% CI, 0.61-0.82, p < 0.00001). All-cause mortality did not differ significantly between groups (RR = 0.80; 95% CI, 0.54-1.18; p = 0.25). Subgroup analysis showed consistent findings across DOAC type, with no significant interaction effects.

Conclusion: Reduced-dose DOACs appear to be as effective as full-dose DOACs in preventing VTE, with a favorable safety profile due to reduced bleeding risk. These findings support reduced-dose DOACs as a viable option for extended anticoagulation in VTE patients.