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

Eur Heart J Qual Care Clin Outcomes. 2024 Jan 12;10(1):55-65. doi: 10.1093/ehjqcco/qcad019.

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.

Keywords: Anticoagulant; Atrial fibrillation; Bleeding; Death; Frailty; Thromboembolism.

MeSH terms

  • Administration, Oral
  • Anticoagulants / adverse effects
  • Atrial Fibrillation* / complications
  • Atrial Fibrillation* / drug therapy
  • Cohort Studies
  • Dabigatran / adverse effects
  • Frailty* / complications
  • Frailty* / epidemiology
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology
  • Humans
  • Pyridines*
  • Rivaroxaban / therapeutic use
  • Stroke* / epidemiology
  • Stroke* / etiology
  • Stroke* / prevention & control
  • Thiazoles*
  • Warfarin / therapeutic use

Substances

  • Anticoagulants
  • edoxaban
  • Rivaroxaban
  • Dabigatran
  • Warfarin
  • Pyridines
  • Thiazoles