Frailty and subsequent adverse outcomes in older patients with atrial fibrillation treated with oral anticoagulants: The Shizuoka study

Background: In older patients with atrial fibrillation (AF), frailty is frequently prevalent. However, the prognostic value of frailty for adverse events after initiation of oral anticoagulants (OACs) is unclear. Objectives: We assessed whether frailty at the time of OAC initiation is associated with subsequent bleeding or embolic events. Methods: We extracted patients aged ≥65 years with nonvalvular AF in whom OACs were initiated from a universal administrative claims database incorporating primary and hospital care records in Shizuoka, Japan, between 2012 and 2018. Frailty was assessed using the electronic frailty index (eFI). The association of frailty with bleeding events and ischemic stroke/transient ischemic attack were evaluated using the Fine-Gray model and restricted cubic spline model. Results: Among 12,585 patients with AF, 7.8% were categorized as fit, 31.5% as mildly frail, 34.8% as moderately frail, and 25.9% as severely frail. The risk of bleeding was associated with a higher eFI (adjusted subdistribution hazard ratio 95% CI for fit or mild frailty: 1.15 1.02-1.30; moderate frailty: 1.42 1.24-1.61; and severe frailty: 1.86 1.61-2.15), whereas the association was weaker for ischemic stroke/transient ischemic attack. The spline models demonstrated that the relative hazard for bleeding increased steeply with increasing eFI. Conclusion: Patients with frailty in whom OAC therapy is initiated have higher risk of bleeding, highlighting the importance of discussing this increased risk with patients with AF who have frailty and assessing frailty at the time of OAC initiation.