Reduced-dose versus full-dose anticoagulation for extended treatment of VTE
RENOVE trial design and results
Design
Randomised, open-label, non-inferiority trial
Treatment
Reduced-dose direct oral anticoagulant
Control
Full-dose direct oral anticoagulant
Population
2768 patients with venous thromboembolism requiring extended anticoagulation
Follow-up
Median 37.1 months
Primary endpoint
Recurrent venous thromboembolism
Result
Recurrence in 19 of 1383 on reduced dose (5-year cumulative incidence 2.2%, 95% CI 1.1 to 3.3) versus 15 of 1385 on full dose (1.8%, 0.8 to 2.7). Non-inferiority was not met. Clinically relevant bleeding was substantially lower with the reduced dose.
Secondary endpoints
Clinically relevant bleeding, major bleeding, all-cause mortality
In patients with venous thromboembolism requiring extended anticoagulation, reduction of the direct oral anticoagulant dose did not meet the non-inferiority criteria. However, the low recurrence rates in both groups and substantial reduction of clinically relevant bleeding with the reduced dose could support this regimen as an option.
The trial authors, in the published abstract
How it has aged
A trial whose formal verdict and clinical message point in opposite directions, and whose authors say so. Recurrence was rare in both arms; bleeding was not. For most patients on indefinite anticoagulation the trade favours the lower dose, but the trial does not licence that conclusion — it invites it.
Publications
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
Couturaud F, Schmidt J, Sanchez O, 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 Mar 1;405(10480):725-735.
Non-inferiority for recurrent VTE not demonstrated
Absolute recurrence difference small: 2.2% versus 1.8% at five years
Substantially less clinically relevant bleeding on the reduced dose