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 186,132 eligible patients, 41,606 warfarin-apixaban, 30,836 dabigatran-apixaban, and 41,608 rivaroxaban-apixaban pairs were matched. The OACs were associated with a significantly higher risk of all-cause hospitalization compared with apixaban (warfarin: HR = 1.33, 95% CI = 1.27-1.38, P < 0.001; dabigatran: HR = 1.17, 95% CI = 1.11-1.23, P < 0.001; and rivaroxaban: HR = 1.27, 95% CI = 1.22-1.32, P < 0.001) and were associated with a significantly higher risk of hospitalization due to stroke/SE (warfarin: HR = 2.51, 95% CI = 1.92-3.29, P < 0.001; dabigatran: HR = 2.24, 95% CI = 1.60-3.13, P < 0.001; and rivaroxaban: HR = 1.74, 95% CI = 1.31-2.30, P < 0.001). Also, the OACs were associated with significantly higher risk of hospitalization due to MB-related conditions compared with apixaban (warfarin: HR = 1.96, 95% CI = 1.71-2.23, P < 0.001; dabigatran: HR = 1.48; 95% CI = 1.25-1.76, P < 0.001; and rivaroxaban: HR = 2.17, 95% CI = 1.91-2.48, P < 0.001). Compared with apixaban, warfarin ($3,747 vs. $3,061, P < 0.001); dabigatran ($3,230 vs. $2,951, P < 0.001); and rivaroxaban ($3,950 vs. $3,060, P < 0.001) had significantly higher all-cause total health care costs per patient per month. Patients initiating the OACs also had significantly higher stroke/SE- and MB-related medical costs compared with apixaban: warfarin (stroke/SE = $135 vs. $60, P = 0.001; MB = $537 vs. $286, P < 0.001); dabigatran (stroke/SE = $94 vs. $62, P = 0.045; MB = $373 vs. $277, P = 0.010); and rivaroxaban (stroke/SE = $91 vs. $60, P = 0.008; MB = $524 vs. $287, 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 stroke/SE- and MB-related medical costs. DISCLOSURES: This study was funded by Bristol-Myers Squibb and Pfizer. Amin is an employee of the University of California, Irvine, and was a paid consultant to Bristol-Myers Squibb in connection with this study and the development of this manuscript. Keshishian and Zhang are employees of STATinMED Research, a paid consultant to Pfizer and Bristol-Myers Squibb in connection with this study and the development of this manuscript. Trocio, Dina, Mardekian, and Liu are employees of Pfizer, with ownership of stocks in Pfizer. Le, Rosenblatt, Nadkarni, and Vo are employees of Bristol-Myers Squibb. Rosenblatt and Vo have ownership of stocks in Bristol-Myers Squibb. Baser has no conflicts to disclose.