Extended reduced versus full-dose treatment with factor Xa inhibitors in patients with venous thromboembolism: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of cardiovascular-related death. Anticoagulation therapy is effective in preventing recurrence but poses a risk of bleeding. Reduced-dose factor Xa inhibitors (FXI) have been proposed as a long-term strategy to balance efficacy and safety. This systematic review and meta-analysis aims to assess the safety and efficacy of reduced-dose FXIs compared to full-dose FXIs for long-term treatment of VTE. Relevant studies were identified through a comprehensive search in PubMed, Embase, and Cochrane. Studies were included if they were randomized controlled trials (RCTs) comparing reduced-dose and full-dose FXIs for VTE treatment. Statistical analysis was conducted using R software, applying DerSimonian and Laird's random effects model to compute pooled estimates with 95% confidence intervals (CIs). The analysis included five studies with a total of 8421 patients. Reduced-dose DOACs significantly lowered the risk of major and non-major clinically relevant bleeding (CRB) (RR = 0.71; 95%CI = 0.61, 0.82) and clinically relevant non-major bleeding (CRNMB) (RR = 0.75; 95%CI = 0.63, 0.88; P = 0.0006). There was no significant difference in the risk of major bleeding or all-cause death. The risk of thromboembolism recurrence, pulmonary embolism, upper limb DVT, and lower limb DVT was comparable between both groups. Reduced-dose FXIs offer a safer alternative with significantly lower risks of CRB and CRNMB while maintaining similar efficacy to full-dose regimens for preventing thromboembolism recurrence. These findings suggest that reduced-dose FXIs could be beneficial for long-term anticoagulation therapy, particularly in patients at higher risk of bleeding.