Recurrent venous thromboembolism and bleeding during anticoagulation in patients with deep-vein thrombosis treated with vitamin K antagonists or direct oral anticoagulants: insights from the RIETE registry.

Abstract

Randomized trials have shown that direct oral anticoagulants (DOACs) are as effective as vitamin K antagonists (VKAs) for treating venous thromboembolism (VTE), with less major bleeding. Whether these findings apply to routine clinical practice remains uncertain. To compare recurrent VTE and bleeding during anticoagulation in patients with symptomatic lower-limb deep vein thrombosis (DVT) treated with DOACs or VKAs, and to assess outcomes according to approximate eligibility for pivotal randomized trials. We analyzed consecutive patients with symptomatic lower-limb DVT enrolled in the RIETE registry who received therapeutic-dose VKAs or DOACs. Follow-up was restricted to the treatment period. Outcomes were recurrent VTE, major bleeding, and clinically relevant non-major bleeding (CRNMB). Hazard ratios (HRs) were estimated using Cox proportional hazards models with inverse probability of treatment weighting. Among 24,728 patients (11,349 DOACs; 13,379 VKAs), DOACs were associated with lower risks of recurrent VTE (HR 0.71; 95%CI, 0.58-0.87) and major bleeding (HR 0.78; 95%CI, 0.63-0.97), but a higher risk of CRNMB (HR 1.35; 95%CI, 1.17-1.55). Median times to recurrent VTE, major bleeding, and CRNMB were 105, 88, and 81 days, respectively. Among patients approximating eligibility for randomized trials, DOACs were associated with lower risks of recurrent VTE and major bleeding, whereas no significant reduction was observed in trial-ineligible patients. In routine clinical practice, DOACs were associated with lower risks of recurrent VTE and major bleeding, but higher CRNMB rates than VKAs. Their safety advantage appeared more evident in patients with characteristics similar to those enrolled in pivotal randomized trials.