Evidence for Reduced-Dose DOAC in Those at High Risk for VTE Recurrence in Extended Phase Anticoagulation: The RENOVE Trial
Clinical question: Is extended-phase anticoagulation with dose-reduced direct oral anticoagulants (DOACs) as effective and safe as full-dose DOACs in those with venous thromboembolism (VTE) at high risk for VTE recurrence?
Background: The American College of Chest Physicians published guidelines on the treatment of VTE in 2021. These guidelines recommend an extended course of reduced-dose anticoagulation (apixaban or rivaroxaban) for those at high risk of VTE recurrence in those without transient risk factors beyond the initial three months of therapy. However, there is a paucity of high-quality investigations to support the recommendation for dose reduction. The RENOVE trial, published in the Lancet in March 2025, aimed to assess the efficacy and safety of this strategy.
Study design: Non-inferiority, randomized, open-label trial
Setting: 47 hospitals in France
Synopsis: 2,768 adult ambulatory patients with symptomatic VTE (either pulmonary embolus or proximal deep vein thrombosis) who received six to 24 months of uninterrupted full-dose anticoagulation and who were felt to be high risk for recurrence (defined as unprovoked first episode of VTE or expectation of persistent risk factors) were included. Patients were randomized to receive oral treatment with a reduced-dose DOAC (apixaban 2.5 mg twice daily or rivaroxaban 10 mg daily) or a full-dose DOAC (apixaban 5 mg twice daily or rivaroxaban 20 mg daily). Over five years, recurrent VTE occurred at a rate of 2.2% in the reduced-dose group and 1.8% in the full-dose group. Clinically relevant bleeding occurred less in the reduced-dose group (9.9%) compared to the full-dose group (15.2%) over five years. Though the dose reduction did not meet the prespecified criteria for non-inferiority in preventing recurrent VTE in extended-phase anticoagulation, the real-life difference between both groups was small (19 versus 15 patients). Dose reduction, however, resulted in a statistically significant reduction in clinically relevant bleeding (HR, 0.61).
Bottom line: Given relative effectiveness and significant safety benefits, physicians should offer a reduced-dose DOAC for extended-phase treatment of VTE. This is congruent with existing CHEST guidelines on the treatment of VTE.
Citation: Couturaud F, et al. Extended treatment of venous thromboembolism with reduced-dose versus full-dose direct oral anticoagulants in patients at high risk of recurrence: a non-inferiority, multicentre, randomised, open-label, blinded endpoint trial. Lancet. 2025;405(10480):725-735. doi:10.1016/S0140-6736(24)02842-3.
Dr. Clark is a hospitalist and associate program director of the internal medicine residency at Maine Medical Center in Portland, Maine, and an assistant professor at Tufts University School of Medicine in Boston.