The Comparative Effectiveness and Safety of Warfarin, Rivaroxaban, and Apixaban in Patients with Venous Thromboembolism: An Analysis of Three Real-World US Healthcare Databases
Background: Over the past decade, newer direct oral anticoagulants (DOACs), such as rivaroxaban and apixaban, have replaced warfarin for the treatment of venous thromboembolism in the US. However, evidence from studies evaluating multiple oral anticoagulants (OACs) in a head-to-head comparison is limited.
Objectives: To evaluate the comparative effectiveness and safety of three most common VTE treatments: warfarin, rivaroxaban, and apixaban.
Methods: Using three US databases (Optum Clinformatics Data Mart, 2014 – 2020; fee-for-service Medicare and IBM MarketScan, 2014 – 2019), we examined the risk of VTE recurrence and major bleeding in patients hospitalized with VTE who initiated either apixaban, rivaroxaban, or warfarin within 30 days of discharge. We required insurance enrollment for at least 365 days before the index VTE with no anticoagulant prescription or inpatient VTE admission during this time. We conducted as-treated and one-year intention-to-treat (ITT) analysis. Patients were followed from initiation until outcome occurrence, treatment change (discontinuation or switch to another OAC), disenrollment, death, or end of available data. Matching weights, calculated using propensity scores, were used to adjust for confounding. Weighted Cox proportional hazards models, stratified on a database, were used to estimate hazard ratios (HRs) and 95% CIs.
Results: A total of 187,560 VTE patients across the three databases initiated one of the three oral anticoagulants (74,289 apixaban, 52,678 rivaroxaban and 60,593 warfarin initiators). After weighting, mean age was 73.2 years and 58% were female. Patients initiating apixaban had lower rates of VTE recurrence compared with those initiating warfarin (weighted HR 0.70; 95% CI 0.63 to 0.78), or rivaroxaban (HR 0.86; 95% CI 0.77 to 0.96). Similarly, apixaban had lower rates of major bleeding compared with those initiating warfarin (HR 0.68; 95% CI 0.62 to 0.74) or rivaroxaban (HR 0.61; 95% CI 0.56 to 0.66). When comparing warfarin to rivaroxaban, we found that rivaroxaban was associated with lower rates of VTE recurrence (HR 0.81, 95% CI 0.73 to 0.90), but higher rates of major bleeding (HR 1.11, 95% CI 1.02 to 1.20). Results for apixaban were consistent in ITT and across sensitivity analyses. The ITT results for rivaroxaban, however, yielded no association between rivaroxaban and bleeding, when compared to warfarin.
Conclusions: In this study, patients with VTE who initiated apixaban had lower rates for recurrent VTE and bleeding than those initiating warfarin or rivaroxaban. Our findings, in tandem with published literature, suggest that apixaban can be considered as the first line oral anticoagulant in patients with VTE to prevent recurrent events.