Extended Reduced-Dose Direct Oral Anticoagulants for Venous Thromboembolism in Patients with or without Cancer: A Systematic Review and Meta-Analysis

Background Extended treatment with reduced-dose direct oral anticoagulants (DOACs) in patients with venous thromboembolism (VTE) may be more beneficial than full-dose therapy, but this has not yet been conclusively established. Methods We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to September 2025 for randomized controlled trials (RCTs) comparing extended-reduced-dose DOACs with full-dose DOACs in patients with VTE who had completed at least 6 months of anticoagulation. Risk ratios (RR) and 95% confidence intervals (CI) were meta-analyzed using a random-effects model. Results Reduced-dose DOACs showed no significant difference in the risk of recurrent VTE compared with full-dose regimens (RR = 0.94; 95% CI 0.68–1.29). However, reduced-dose DOACs were associated with significantly lower bleeding risk (RR = 0.71; 95% CI, 0.61–0.82), with consistent benefit in both cancer and non-cancer subgroups. Net clinical benefit was comparable between the reduced-dose and full-dose DOAC groups (RR = 0.81; 95% CI, 0.65–1.02). No differences were observed in arterial thromboembolism (RR = 1.13; 95% CI, 0.84–1.52) and all-cause mortality (RR = 0.86; 95% CI, 0.63–1.17). Conclusions Extended treatment with reduced-dose DOACs could be considered superior to full-dose DOACs, as it has a reduced bleeding risk and a similar effect on decreasing recurrent VTE events. Future research should aim to refine dosing strategies, identify specific patient subgroups that may benefit most, and explore individualized treatment approaches to enhance long-term outcomes.