(P-633) Effectiveness and Safety of Direct Oral Anticoagulants versus Warfarin in Patients with Valvular Atrial Fibrillation: A Population-based Cohort Study

Background: Direct oral anticoagulants (DOACs) are increasingly used in place of warfarin, but evidence regarding their effectiveness and safety in patients with valvular atrial fibrillation (AF) remains limited.

Objectives: To assess the effectiveness and safety of DOACs compared to warfarin in patients with valvular AF.

Methods:

Design: New-user retrospective propensity score-matched (PSM) cohort study
Setting: U.S.-based commercial healthcare database from 1 January 2010 to 30 June 2019
Participants: We included adults with valvular AF who were new users of DOACs or warfarin, aged > 18 years at cohort entry. Patients with any of the following during the lookback period were excluded: end-stage renal disease (require dose adjustment), hip or knee replacement (risk of thromboembolic outcomes), a history of stroke or systemic embolism, and those with bioprosthetic or mechanical heart valve replacement.
Measurements: The primary effectiveness outcome was a composite of ischemic stroke or systemic embolism. The primary safety outcome was a composite of intracranial bleeding and gastrointestinal bleeding. We controlled for measured confounders via propensity score matching (PSM) and used Cox proportional-hazards regression with a robust variance estimator to generate marginal hazard ratios (HRs) and corresponding confidence intervals (CIs).

Results: Among a total of 56,336 PSM patients with valvular AF, 787 patients had stroke or systemic embolism among 28,168 DOACs users (3.9 events per 100 person-years), compared with 1,211 among 28,168 warfarin users (6.0 events per 100 person-years, HR, 0.64; 95% CI 0.59–0.70). In the matched sample, 1,465 patients had a major bleeding among 28,168 DOACs users (7.1 events per 100 person-years), compared with 2,155 among 28,168 warfarin users (10.6 events per 100 person-years) (HR, 0.67; 95% CI 0.63–0.72). The results for the effectiveness and safety outcome remained consistent with apixaban (HR, 0.54, 95%CI 0.47–0.61 and HR, 0.52, 95%CI 0.47–0.57) and rivaroxaban (HR, 0.74, CI 0.64–0.86 and HR, 0.87, CI 0.79–0.96), and for the major bleeding outcome with dabigatran (HR, 0.81, 95%CI 0.68–0.97) but not for effectiveness (HR, 1.03, 95%CI 0.81–1.31).

Conclusions: In this comparative effectiveness study using practice-based claims data, patients with valvular AF who were new-users of DOACs had a lower risk of ischemic stroke or systemic embolism and major bleeding compared with warfarin. These data may be used to guide risk-benefit discussions regarding anticoagulant choices for patients with valvular AF.