Outcomes Associated With Apixaban Use in Patients With End-Stage Kidney Disease and Atrial Fibrillation in the United States

Circulation. 2018 Oct 9;138(15):1519-1529. doi: 10.1161/CIRCULATIONAHA.118.035418.


Background: Patients with end-stage kidney disease (ESKD) on dialysis were excluded from clinical trials of direct oral anticoagulants for atrial fibrillation (AF). Recent data have raised concerns regarding the safety of dabigatran and rivaroxaban, but apixaban has not been evaluated despite current labeling supporting its use in this population. The goal of this study was to determine patterns of apixaban use and its associated outcomes in dialysis-dependent patients with ESKD and AF.

Methods: We performed a retrospective cohort study of Medicare beneficiaries included in the United States Renal Data System (October 2010 to December 2015). Eligible patients were those with ESKD and AF undergoing dialysis who initiated treatment with an oral anticoagulant. Because of the small number of dabigatran and rivaroxaban users, outcomes were only assessed in patients treated with apixaban or warfarin. Apixaban and warfarin patients were matched (1:3) based on prognostic score. Differences between groups in survival free of stroke or systemic embolism, major bleeding, gastrointestinal bleeding, intracranial bleeding, and death were assessed using Kaplan-Meier analyses. Hazard ratios (HRs) and 95% CIs were derived from Cox regression analyses.

Results: The study population consisted of 25 523 patients (45.7% women; 68.2±11.9 years of age), including 2351 patients on apixaban and 23 172 patients on warfarin. An annual increase in apixaban prescriptions was observed after its marketing approval at the end of 2012, such that 26.6% of new anticoagulant prescriptions in 2015 were for apixaban. In matched cohorts, there was no difference in the risks of stroke/systemic embolism between apixaban and warfarin (HR, 0.88; 95% CI, 0.69-1.12; P=0.29), but apixaban was associated with a significantly lower risk of major bleeding (HR, 0.72; 95% CI, 0.59-0.87; P<0.001). In sensitivity analyses, standard-dose apixaban (5 mg twice a day; n=1034) was associated with significantly lower risks of stroke/systemic embolism and death as compared with either reduced-dose apixaban (2.5 mg twice a day; n=1317; HR, 0.61; 95% CI, 0.37-0.98; P=0.04 for stroke/systemic embolism; HR, 0.64; 95% CI, 0.45-0.92; P=0.01 for death) or warfarin (HR, 0.64; 95% CI, 0.42-0.97; P=0.04 for stroke/systemic embolism; HR, 0.63; 95% CI, 0.46-0.85; P=0.003 for death).

Conclusions: Among patients with ESKD and AF on dialysis, apixaban use may be associated with a lower risk of major bleeding compared with warfarin, with a standard 5 mg twice a day dose also associated with reductions in thromboembolic and mortality risk.

Keywords: anticoagulation; atrial fibrillation; bleeding; dialysis; stroke prevention.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / mortality
  • Databases, Factual
  • Factor Xa Inhibitors / administration & dosage*
  • Factor Xa Inhibitors / adverse effects
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Kidney Failure, Chronic / diagnosis
  • Kidney Failure, Chronic / mortality
  • Kidney Failure, Chronic / therapy*
  • Male
  • Medicare
  • Middle Aged
  • Pyrazoles / administration & dosage*
  • Pyrazoles / adverse effects
  • Pyridones / administration & dosage*
  • Pyridones / adverse effects
  • Renal Dialysis* / adverse effects
  • Renal Dialysis* / mortality
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • United States / epidemiology


  • Factor Xa Inhibitors
  • Pyrazoles
  • Pyridones
  • apixaban