• Dae Hyun Kim, Ajinkya Pawar, Joshua J Gagne, Lily G Bessette, Hemin Lee, Robert J Glynn, and Sebastian Schneeweiss.
• Brigham and Women's Hospital, Harvard Medical School, Hebrew SeniorLife, and Beth Israel Deaconess Medical Center, Boston, Massachusetts (D.H.K.).
• Ann. Intern. Med. 2021 Sep 1; 174 (9): 1214-1223.

BackgroundThe role of differing levels of frailty in the choice of oral anticoagulants for older adults with atrial fibrillation (AF) is unclear.ObjectiveTo examine the outcomes of direct oral anticoagulants (DOACs) versus warfarin by frailty levels.Design1:1 propensity score-matched analysis of Medicare data, 2010 to 2017.SettingCommunity.PatientsMedicare beneficiaries with AF who initiated use of dabigatran, rivaroxaban, apixaban, or warfarin.MeasurementsComposite end point of death, ischemic stroke, or major bleeding by frailty levels, defined by a claims-based frailty index.ResultsIn 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.LimitationsResidual confounding and lack of clinical frailty assessment.ConclusionFor 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 SourceNational Institute on Aging.

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