Outcomes of apixaban versus warfarin in patients with atrial fibrillation and multi-morbidity: Insights from the ARISTOTLE trial

Am Heart J. 2019 Feb:208:123-131. doi: 10.1016/j.ahj.2018.09.017. Epub 2018 Nov 22.

Abstract

Background: Patients with atrial fibrillation (AF) often have multi-morbidity, defined as ≥3 comorbid conditions. Multi-morbidity is associated with polypharmacy, adverse events, and frailty potentially altering response to anticoagulation. We sought to describe the prevalence of multi-morbidity among older patients with AF and determine the association between multi-morbidity, clinical outcomes, and the efficacy and safety of apixaban compared with warfarin.

Methods: In this post-hoc subgroup analysis of the ARISTOTLE trial, we studied enrolled patients age ≥ 55 years (n = 16,800). Patients were categorized by the number of comorbid conditions at baseline: no multi-morbidity (0-2 comorbid conditions), moderate multi-morbidity (3-5 comorbid conditions), and high multi-morbidity (≥6 comorbid conditions). Association between multi-morbidity and clinical outcomes were analyzed by treatment with a median follow-up of 1.8 (1.3-2.3) years.

Results: Multi-morbidity was present in 64% (n = 10,713) of patients; 51% (n = 8491) had moderate multi-morbidity, 13% (n = 2222) had high multi-morbidity, and 36% (n = 6087) had no multi-morbidity. Compared with the no multi-morbidity group, the high multi-morbidity group was older (74 vs 69 years), took twice as many medications (10 vs 5), and had higher CHA2DS2-VASc scores (4.9 vs 2.7) (all P < .001). Adjusted rates per 100 patient-years for stroke/systemic embolism, death, and major bleeding increased with multi-morbidity (Reference no multi-morbidity; moderate multi-morbidity 1.42 [1.24-1.64] and high multi-morbidity 1.92 [1.59-2.31]), with no interaction in relation to efficacy or safety of apixaban.

Conclusions: Multi-morbidity is prevalent among the population with AF; efficacy and safety of apixaban is preserved in this subgroup supporting extension of trial results to the most complex AF patients.

Trial registration: ClinicalTrials.gov NCT00412984.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants / therapeutic use*
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / epidemiology*
  • Double-Blind Method
  • Embolism / epidemiology*
  • Embolism / etiology
  • Embolism / prevention & control
  • Factor Xa Inhibitors / therapeutic use*
  • Female
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology*
  • Hemorrhage / prevention & control
  • Humans
  • Male
  • Middle Aged
  • Multimorbidity*
  • Polypharmacy
  • Pyrazoles / therapeutic use*
  • Pyridones / therapeutic use*
  • Stroke / epidemiology*
  • Stroke / etiology
  • Stroke / prevention & control
  • Warfarin / therapeutic use*

Substances

  • Anticoagulants
  • Factor Xa Inhibitors
  • Pyrazoles
  • Pyridones
  • apixaban
  • Warfarin

Associated data

  • ClinicalTrials.gov/NCT00412984