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

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 2013-2019 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 to 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 to VKAs. Apixaban was associated with lower major bleeding risks compared to 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 to dabigatran and edoxaban.

CONCLUSION: Frailty was an independent risk factor of death. NOACs had better benefit-risk profiles than VKAs in patients with frailty, especially apixaban, followed by edoxaban.