Reduced-Dose vs Full-Dose Direct Oral Anticoagulants for Extended Anticoagulation Therapy in Patients With Venous...

Extended anticoagulation therapy is often required in patients with venous thromboembolism (VTE), but the optimal dosing strategy remains unclear. This study aimed to evaluate the efficacy and safety of reduced-dose versus full-dose direct oral anticoagulants in the extended treatment of VTE.

We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials (RCT) comparing reduced-dose versus full-dose direct oral anticoagulants for extended anticoagulation therapy in VTE. Primary outcomes included major bleeding, recurrent VTE, all-cause mortality, and clinically relevant nonmajor bleeding. Secondary outcomes included pulmonary embolism and upper limb deep vein thrombosis. Statistical analysis was performed using R 4.4.2. Quality assessment of included RCT was conducted using the Cochrane Risk of Bias 2 tool.

We included 8781 patients from 5 RCT with 50.1% (n = 4395) receiving reduced-dose anticoagulation; 21.7% (n = 1908) had active cancer, and 18.1% (n = 1585) had a history of previous deep vein thrombosis/pulmonary embolism. Major bleeding (1.2% vs 2.0%; risk ratio [RR], 0.62; 95% CI, 0.42-0.92; P = .019) and clinically relevant nonmajor bleeding (5.2% vs 7.0%; RR, 0.75; 95% CI, 0.63-0.88; P < .001) were significantly lower in the reduced-dose group. There was no significant difference in all-cause mortality (4.9% vs 5.8%; RR, 0.86; 95% CI, 0.63-1.17; P = .346) and recurrent VTE (2.0% vs 2.2%; RR, 0.92; 95% CI, 0.70-1.23; P = .587) between the 2 groups. All included studies were assessed as having an overall low risk of bias.

Reduced-dose anticoagulation demonstrates significantly lower bleeding risk compared to full-dose in VTE patients, with comparable efficacy in preventing recurrent VTE and mortality.