A real-world observational study of hospitalization and health care costs among nonvalvular atrial fibrillation patients prescribed oral anticoagulants in the U.S. Medicare population

Abstract

BACKGROUND: Clinical trials have shown that direct oral anticoagulants (DOACs)—including dabigatran, rivaroxaban, apixaban, and edoxaban—are at least as effective and safe as warfarin for the risk of stroke/systemic embolism (SE) and major bleeding (MB) in patients with atrial fibrillation (AF). However, few studies have compared oral anticoagulants (OACs) among elderly patients. OBJECTIVE: To compare hospitalization risks (all-cause, stroke/SE-related, and MB-related) and associated health care costs among elderly nonvalvular AF (NVAF) patients in the Medicare population who initiated warfarin, dabigatran, rivaroxaban, or apixaban. METHODS: Patients (aged ≥65 years) initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from the Centers for Medicare & Medicaid Services database from January 1, 2013, to December 31, 2014. Patients initiating each OAC were matched 1:1 to apixaban patients using propensity score matching to balance demographic and clinical characteristics. Cox proportional hazards models were used to estimate the risk of hospitalization of each OAC versus apixaban. Generalized linear models and two-part models with bootstrapping were used to compare all-cause health care costs and stroke/SE- and MB-related medical costs between matched cohorts. RESULTS: Of the 264,479 eligible patients, 77,480 warfarin-apixaban, 41,580 dabigatran-apixaban, and 77,640 rivaroxaban-apixaban patients were matched. The OACs were associated with a significantly higher risk of all-cause hospitalization compared with apixaban (warfarin: HR=1.27, 95% CI=1.23-1.31, P<0.001; dabigatran: HR=1.13, 95% CI=1.08-1.18, P<0.001; and rivaroxaban: HR=1.22, 95% CI=1.18-1.26, P<0.001) and were associated with a significantly higher risk of hospitalization due to stroke/SE (warfarin: HR=2.18, 95% CI=1.80-2.64, P<0.001; dabigatran: HR=1.45, 95% CI=1.12-1.88, P=0.006; and rivaroxaban: HR=1.40, 95% CI=1.14-1.71, P=0.001). Also, the OACs were associated with significantly higher risk of hospitalization due to MB-related conditions compared with apixaban (warfarin: HR=1.76, 95% CI=1.59-1.95, P<0.001; dabigatran: HR=1.44, 95% CI=1.23-1.68, P<0.001; and rivaroxaban: HR=1.89, 95% CI=1.71-2.09, P<0.001). Compared with apixaban, warfarin ($3,577 vs. $3,183, P<0.001); dabigatran ($3,217 vs. $3,060, P<0.001); and rivaroxaban ($3,878 vs. $3,180, P<0.001) had significantly higher all-cause total health care costs per patient per month. Patients initiating the OACs had significantly higher MB-related medical costs compared with apixaban: warfarin ($472 vs. $269; P<0.001); dabigatran ($364 vs. $245, P<0.001); and rivaroxaban ($493 vs. $270, P<0.001). Warfarin was also associated with higher stroke/SE-related medical costs compared with apixaban ($124 vs. $62, P<0.001). CONCLUSIONS: This real-world study showed that among elderly NVAF patients in the Medicare population, apixaban was associated with significantly lower risks of all-cause, stroke/SE-related, and MB-related hospitalizations compared with warfarin, dabigatran, and rivaroxaban. Accordingly, apixaban showed significantly lower all-cause health care costs and MB-related medical costs.