Frailty and Clinical Outcomes of Direct Oral Anticoagulants Versus Warfarin in Older Adults With Atrial Fibrillation

Background: The role of differing levels of frailty in the choice of oral anticoagulants for older adults with atrial fibrillation (AF) is unclear. Objective: To examine the outcomes of direct oral anticoagulants (DOACs) versus warfarin by frailty levels. Design: 1:1 propensity score–matched analysis of Medicare data, 2010 to 2017. Setting: Community. Patients: Medicare beneficiaries with AF who initiated use of dabigatran, rivaroxaban, apixaban, or warfarin. Measurements: Composite end point of death, ischemic stroke, or major bleeding by frailty levels, defined by a claims-based frailty index. Results: In the dabigatran–warfarin cohort (n = 158 730; median follow-up, 72 days), the event rate per 1000 person-years was 63.5 for dabigatran initiators and 65.6 for warfarin initiators (hazard ratio [HR], 0.98 [95% CI, 0.92 to 1.05]; rate difference [RD], −2.2 [CI, −6.5 to 2.1]). For nonfrail, prefrail, and frail persons, HRs were 0.81 (CI, 0.68 to 0.97), 0.98 (CI, 0.90 to 1.08), and 1.09 (CI, 0.96 to 1.23), respectively. In the rivaroxaban–warfarin cohort (n = 275 944; median follow-up, 82 days), the event rate per 1000 person-years was 77.8 for rivaroxaban initiators and 83.7 for warfarin initiators (HR, 0.98 [CI, 0.94 to 1.02]; RD, −5.9 [CI, −9.4 to −2.4]). For nonfrail, prefrail, and frail persons, HRs were 0.88 (CI, 0.77 to 0.99), 1.04 (CI, 0.98 to 1.10), and 0.96 (CI, 0.89 to 1.04), respectively. In the apixaban–warfarin cohort (n = 218 738; median follow-up, 84 days), the event rate per 1000 person-years was 60.1 for apixaban initiators and 92.3 for warfarin initiators (HR, 0.68 [CI, 0.65 to 0.72]; RD, −32.2 [CI, −36.1 to −28.3]). For nonfrail, prefrail, and frail persons, HRs were 0.61 (CI, 0.52 to 0.71), 0.66 (CI, 0.61 to 0.70), and 0.73 (CI, 0.67 to 0.80), respectively. Limitations: Residual confounding and lack of clinical frailty assessment. Conclusion: For older adults with AF, apixaban was associated with lower rates of adverse events across all frailty levels. Dabigatran and rivaroxaban were associated with lower event rates only among nonfrail patients. Primary Funding Source: National Institute on Aging.