Reduced-Dose Versus Full-Dose Direct Oral Anticoagulants for Extended Treatment of Venous Thromboembolism

BackgroundVenous thromboembolism (VTE) often necessitates extended anticoagulation to reduce the risk of recurrence. While direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists due to their improved safety and convenience, the optimal long-term dosing strategy (reduced vs full dose) remains uncertain. This systematic review assesses the efficacy and safety outcomes of reduced-dose DOACs compared with full-dose therapy for extended VTE treatment.MethodsWe conducted a systematic review of randomized controlled trials (RCTs) comparing reduced-dose and full-dose DOACs in patients with VTE. Due to heterogeneity in study designs and outcomes, a narrative synthesis was performed.ResultsThree RCTs were included. In AMPLIFY-EXT, recurrent VTE or death occurred in 1.7% of patients receiving apixaban (both 2.5 mg and 5 mg) versus 8.8% with placebo. In EINSTEIN CHOICE, recurrent VTE occurred in 1.2% and 1.5% of patients receiving rivaroxaban 10 mg and 20 mg, respectively, compared with 4.4% with aspirin. The safety outcomes were comparable between the two DOAC doses in AMPLIFY-EXT and EINSTEIN CHOICE. RENOVE reported 5-year cumulative incidences of recurrent VTE of 2.2% with reduced-dose and 1.8% with full-dose DOACs (hazard ratio 1.32, 95% confidence interval [CI]: 0.67-2.60; P = .23 for non-inferiority). Major or clinically relevant non-major bleeding events occurred in 9.9% patients in the reduced-dose group and 15.2% patients in the full-dose group (HR 0.61; 95% CI 0.48-0.79).ConclusionCurrent evidence suggest that reduced-dose DOACs provide efficacy comparable to full-dose regimens without a corresponding increase in bleeding events in the extended treatment of VTE.