Extended Treatment with Reduced-Dose Direct Oral Anticoagulants for Venous Thromboembolism: Systematic Review and...

Extended anticoagulation reduces recurrent venous thromboembolism (VTE) risk but increases bleeding, creating uncertainty regarding optimal dosing. Direct oral anticoagulants (DOACs) are preferred for long-term therapy; however, it is unclear whether reduced-dose regimens are noninferior for recurrence prevention and safer regarding clinically relevant bleeding compared with full-dose therapy.

PubMed, Embase, and Cochrane Library were searched for randomized controlled trials (RCTs) comparing reduced- vs full-dose DOACs in extended anticoagulation. Bayesian random-effects meta-analysis was performed using a vague prior for treatment effect (normal [0,2.72]) and an informative prior for heterogeneity (log-normal [-1.975,0.895]), with sensitivity analyses using weakly informative and vague priors. The noninferiority margin was odds ratio (OR) < 1.48, based on previous a meta-analysis result. Analyses were conducted in R 4.4.2.

Five RCTs with 8781 patients were included. Reduced-dose treatment had a posterior probability of superiority (OR < 1) of 61.45% to 63.54% and probability of noninferiority (OR < 1.48) of 97.27% to 99.23% for recurrent VTE (average OR, 0.94; 95% credible interval [CrI], 0.66-1.35). For clinically relevant bleeding, the probability of superiority ranged between 98.95% and 99.82% (OR, 0.69; 95% CrI, 0.56-0.85). Comparable efficacy and safety were observed in patients with active cancer, < 75 years, body mass index (BMI) < 30, and male patients; however, results in the active cancer population depended on priors choice. Low noninferiority probabilities were observed in older patients, patients with obesity, and female patients.

Bayesian analysis indicates high probabilities of noninferiority and safety in the overall cohort, male patients, younger individuals, and nonobese patients, supporting its use as an effective and safer long-term strategy. Therefore, extended reduced-dose DOAC therapy is safer and noninferior to full-dose therapy for preventing recurrent VTE.

PROSPERO CRD420251088203.