Clinical characteristics, prescription patterns and clinical outcomes of patients with extended therapy with direct oral anticoagulants for unprovoked venous thromboembolism

Background: Extended therapy with direct oral anticoagulants (DOACs) is common for managing unprovoked venous thromboembolism (VTE), but real-world data on dosing decisions and their association with outcomes are limited. Methods: From April 2013 to September 2023, we identified patients with unprovoked VTE in the RIETE registry who survived the first 6 months without recurrent VTE or major bleeding. We examined predictors of reduced- vs. full-dose DOACs (rivaroxaban or apixaban) and the association between dosing and recurrent VTE and major bleeding. Logistic regression was used to identify predictors of dosing and competing-risk regression models to identify predictors of outcomes. Results: Among 3749 patients undergoing extended DOAC therapy, 921 (25%) received reduced doses. Predictors of reduced-dose use included age >75 years [adjusted odds ratio (aOR): 1.74; 95%CI: 1.48-2.05], body weight <60 kg (aOR: 1.36; 95%CI: 1.08-1.71), renal failure (aOR: 1.78; 95%CI: 1.41-2.24), and apixaban (vs. rivaroxaban) use (aOR: 2.33; 95%CI: 1.80-3.00). Over a median of 240 days, among all 3749 patients, 44 developed VTE recurrence and 15 bled. Apixaban (vs. rivaroxaban) use [adjusted hazard ratio (aHR): 0.42; 95%CI: 0.40-0.45] and antiplatelet therapy (aHR: 1.72; 95%CI: 1.68-1.77) were associated with VTE recurrence. Male sex (aHR: 0.70; 95%CI: 0.65-0.76), weight <60 kg (aHR: 2.02; 95%CI: 1.91-2.14), renal failure (aHR: 2.76; 95%CI: 2.72-2.81), reduced- (vs. full-dose) DOACs (aHR: 0.83; 95%CI: 0.80-0.87) and antiplatelet use (aHR: 8.18; 95%CI: 7.89-8.47) were associated with major bleeding. Conclusions: We highlight a mismatch between dosing decisions and clinical outcomes, suggesting a need for more outcome-focused strategies in DOAC prescribing.