A new study showed that reducing the dose of direct oral anticoagulants for extended venous thromboembolism treatment could lower bleeding risk but didn't meet noninferiority criteria for preventing recurrence.
In the RENOVE trial, published in The Lancet and conducted across 47 French hospitals, researchers enrolled 2,768 patients with acute symptomatic venous thromboembolism (VTE) who had received 6 to 24 months of full-dose anticoagulation. The patients were randomly assigned to either a reduced dose of apixaban (2.5 mg twice daily) or rivaroxaban (10 mg once daily) or a full dose of apixaban (5 mg twice daily) or rivaroxaban (20 mg once daily).
At a median follow-up of 37.1 months, recurrent VTE occurred in 19 patients in the reduced-dose group (5-year cumulative incidence = 2.2%) compared with 15 patients in the full-dose group (1.8%), resulting in a hazard ratio (HR) of 1.32 (95% confidence interval [CI] = 0.67–2.60, P = .23), failing to exclude the predefined noninferiority margin of 1.7. Major or clinically relevant nonmajor bleeding was significantly lower in the reduced-dose group at 9.9% vs 15.2% in the full-dose group, yielding an adjusted HR of 0.61 (95% CI = 0.48–0.79).
All-cause mortality was 4.3% in the reduced-dose group and 6.1% in the full-dose group, with similar VTE- or bleeding-related deaths. While noninferiority was not established, the lower bleeding risk suggested dose reduction could be considered among patients at high bleeding risk.
"Although reduction of the direct oral anticoagulant dose in patients with [VTE] requiring extended anticoagulation did not meet the study noninferiority criteria, the rates of recurrent [VTE] were low in both groups," said lead study author Francis Couturaud, MD, PhD, of the Centre Hospitalier Universitaire Brest in France, and colleagues.
Supported by the French Ministry of Health, the researchers emphasized the need for further studies to refine long-term anticoagulation strategies. The findings contributed to ongoing discussions on balancing efficacy and safety in extended VTE treatment.
No conflicts of interest were disclosed.
