3F-06 - Oral Anticoagulation and Risk of Adverse Clinical Outcomes in Patients with Venous Thromboembolism

Background: Venous thromboembolism (VTE) is a common condition affecting millions of patients in the world annually. Over the past decade, there has been a significant shift in the use of pharmacologic agents for VTE, with direct oral anticoagulants (OAC) replacing warfarin as the drugs of choice for VTE recurrence prevention; however, evidence from head-to-head comparison studies remains limited.

Objectives: To compare the safety and effectiveness of three common OACs (apixaban, rivaroxaban, and warfarin) in patients with VTE.

Methods: We conducted a population-based cohort study using two US private and Medicare health insurance databases, covering 2016-2024 period. The study included adults aged 18 and older with at least one year of continuous insurance enrollment prior to OAC initiation. Patients were required to initiate OAC within 30 days of discharge from initial VTE hospitalization and had no history of VTE in the year before cohort entry. Exposure groups were defined based on the initial pharmacy-dispensed OAC. The primary effectiveness outcome was hospitalization for recurrent VTE, and the primary safety outcome was major bleeding. Follow-up began on the date after OAC initiation and continued until the occurrence of outcome, treatment discontinuation or switch, disenrollment from insurance plan, death, or end of the study period, whichever occurred first. To adjust for confounding, propensity score (PS) matching weights were applied to balance baseline characteristics across the three treatment groups. Weighted Cox hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI).

Results: After PS adjustment, we identified 163,593 eligible individuals (mean age 71.4 years; 92,800 [56.7%] female), and 95,734 (58.5%) initiated apixaban, 42,006 (25.7%) rivaroxaban, and 25,853 (15.8%) warfarin. Overall, 3,270 recurrent VTE and 4,229 bleeding events occurred. Compared with warfarin, patients on apixaban (HR 0.67, 95% CI 0.61–0.75) and rivaroxaban (HR 0.77, 95% CI 0.69–0.87) had a lower risk of recurrent VTE. Apixaban showed a further decrease in recurrent VTE risk compared with rivaroxaban (HR 0.87, 95% CI 0.78–0.96). Patients on apixaban also had a lower risk of major bleeding compared with warfarin (HR 0.70, 95% CI 0.64–0.76) and rivaroxaban (HR 0.69, 95% CI 0.63–0.75). No difference in bleeding risk was observed between rivaroxaban and warfarin (HR 1.02, 95% CI 0.92-1.12). Results were consistent across sensitivity and subgroup analyses.

Conclusions: In this large-scale cohort study comparing the three most frequently prescribed OAC, we observed that patients with VTE who initiated apixaban had lower rates of hospitalization for recurrent VTE and major bleeding compared to patients who initiated rivaroxaban or warfarin.