Background: Low-dose direct oral anticoagulants (DOACs) have been studied in randomized controlled trials for extended prevention of venous thromboembolism (VTE) after 6 months at therapeutic doses.
Objectives: This study examined the effectiveness, safety, and utilization of low-dose DOACs in a real-world cohort with dedicated analysis of cancer patients.
Methods: Consecutive patients enrolled in the Mayo Clinic VTE Registry from March 1, 2013, to December 31, 2022, were followed prospectively for VTE recurrence, major bleeding (MB), and clinically relevant non-MB (CRNMB). Patients with events during the first 3 months were excluded. After anticoagulation for 3 months with either rivaroxaban or apixaban, characteristics and outcomes of patients continuing anticoagulation were evaluated by Cox regression and a nested case-control study.
Results: In total, 466 patients (71% apixaban and 29% rivaroxaban) were identified on low-dose DOACs and 2273 in the full-dose group. Demographics between groups were mostly similar. Patients with active cancer as a provoking factor were less common in the overall low-dose DOAC group. In Cox regression analysis, VTE recurrence was not different between any groups. In noncancer patients, CRNMB but not MB was decreased in the low-dose group (hazard ratio [HR], 4.97; P < .001). In patients with cancer, low-dose DOACs were protective for MB (HR, 4.48; P = .001) and CRNMB (HR, 6.81; P < .001). Bleeding outcomes were the same in nested case-control analysis as well.
Conclusion: Dose reduction maintains low recurrence rates but also decreases bleeding, with the most pronounced effect in the cancer population.
Keywords: Factor Xa inhibitors; anticoagulation; bleeding; cancer-associated thrombus; direct oral anticoagulants; venous thromboembolism.
© 2025 The Authors.