Oral anticoagulants for nonvalvular atrial fibrillation in frail elderly patients: insights from the ARISTOPHANES study

J Intern Med. 2021 Jan;289(1):42-52. doi: 10.1111/joim.13140. Epub 2020 Jul 16.


Background: Patient frailty amongst patients with nonvalvular atrial fibrillation (NVAF) is associated with adverse health outcomes and increased risk of mortality. Additional evidence is needed to evaluate effective and safe NVAF treatment in this patient population.

Objectives: This subgroup analysis of the ARISTOPHANES study compared the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) amongst frail NVAF patients prescribed nonvitamin K antagonist oral anticoagulants (NOACs) or warfarin.

Methods: This comparative retrospective observational study of frail, older NVAF patients who initiated apixaban, dabigatran, rivaroxaban or warfarin from 01JAN2013-30SEP2015 was conducted using Medicare and 3 US commercial claims databases. To compare each drug, 6 propensity score-matched (PSM) cohorts were created. Patient cohorts were pooled from 4 databases after PSM. Cox models were used to estimate hazard ratios (HR) of S/SE and MB.

Results: Amongst NVAF patients, 34% (N = 150 487) met frailty criteria. Apixaban and rivaroxaban were associated with a lower risk of S/SE vs warfarin (apixaban: HR: 0.61, 95% CI: 0.55-0.69; rivaroxaban: HR: 0.79, 95% CI: 0.72-0.87). For MB, apixaban (HR: 0.62, 95% CI: 0.57-0.66) and dabigatran (HR: 0.79, 95% CI: 0.70-0.89) were associated with a lower risk and rivaroxaban (HR: 1.14, 95% CI: 1.08-1.21) was associated with a higher risk vs warfarin.

Conclusion: Amongst this cohort of frail NVAF patients, NOACs were associated with varying rates of stroke/SE and MB compared with warfarin. Due to the lack of real-world data regarding OAC treatment in frail patients, these results may inform clinical practice in the treatment of this patient population.

Keywords: anticoagulation treatment; atrial fibrillation; cardiology; stroke; warfarin.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Anticoagulants / adverse effects*
  • Anticoagulants / therapeutic use
  • Atrial Fibrillation / drug therapy*
  • Cause of Death
  • Dabigatran / adverse effects
  • Frail Elderly*
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology*
  • Humans
  • Propensity Score
  • Pyrazoles / adverse effects
  • Pyridones / adverse effects
  • Retrospective Studies
  • Risk Factors
  • Rivaroxaban / adverse effects
  • Stroke / chemically induced
  • Stroke / epidemiology*
  • United States / epidemiology
  • Vitamin K / antagonists & inhibitors
  • Warfarin / adverse effects


  • Anticoagulants
  • Pyrazoles
  • Pyridones
  • Vitamin K
  • apixaban
  • Warfarin
  • Rivaroxaban
  • Dabigatran