Impact of frailty on the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation: a nationwide cohort study

Abstract Aims Data on non-vitamin K antagonist oral anticoagulants (NOACs) use in patients with atrial fibrillation (AF) and frailty are scarce. Therefore, the impact of frailty on AF-related outcomes and benefit–risk profiles of NOACs in patients with frailty were investigated. Methods and results AF patients initiating anticoagulation between 2013 and 2019 were included using Belgian nationwide data. Frailty was assessed with the Claims-based Frailty Indicator. Among 254 478 anticoagulated AF patients, 71 638 (28.2%) had frailty. Frailty was associated with higher all-cause mortality risks [adjusted hazard ratio (aHR) 1.48, 95% confidence interval (CI) (1.43–1.54)], but not with thromboembolism or bleeding. Among subjects with frailty (78 080 person-years of follow-up), NOACs were associated with lower risks of stroke or systemic embolism (stroke/SE) [aHR 0.77, 95%CI (0.70–0.86)], all-cause mortality [aHR 0.88, 95%CI (0.84–0.92)], and intracranial bleeding [aHR 0.78, 95%CI (0.66–0.91)], a similar major bleeding risk [aHR 1.01, 95%CI (0.93–1.09)], and higher gastrointestinal bleeding risk [aHR 1.19, 95%CI (1.06–1.33)] compared with VKAs. Major bleeding risks were lower with apixaban [aHR 0.84, 95%CI (0.76–0.93)], similar with edoxaban [aHR 0.91, 95%CI (0.73–1.14)], and higher with dabigatran [aHR 1.16, 95%CI (1.03–1.30)] and rivaroxaban [aHR 1.11, 95%CI (1.02–1.21)] compared with VKAs. Apixaban was associated with lower major bleeding risks compared with dabigatran [aHR 0.72, 95%CI (0.65–0.80)], rivaroxaban [aHR 0.78, 95%CI (0.72–0.84)] and edoxaban [aHR 0.74, 95%CI (0.65–0.84)], but mortality risk was higher compared with dabigatran and edoxaban. Conclusion Frailty was an independent risk factor of death. Non-vitamin K antagonist oral anticoagulants had better benefit–risk profiles than VKAs in patients with frailty, especially apixaban, followed by edoxaban. Graphical Abstract Graphical Abstract AF: atrial fibrillation; aHR: adjusted hazard ratio; Api: apixaban; CI: confidence interval; Dabi: dabigatran; Edo: edoxaban; IPTW: inverse probability of treatment weighting; NOAC: non-vitamin K antagonist oral anticoagulant; OAC: oral anticoagulant; Ref: reference category; Riva: rivaroxaban; SE: systemic embolism; VKA: vitamin K antagonist.