Digoxin and Mortality in Patients With Atrial Fibrillation

J Am Coll Cardiol. 2018 Mar 13;71(10):1063-1074. doi: 10.1016/j.jacc.2017.12.060.

Abstract

Background: Digoxin is widely used in patients with atrial fibrillation (AF).

Objectives: The goal of this paper was to explore whether digoxin use was independently associated with increased mortality in patients with AF and if the association was modified by heart failure and/or serum digoxin concentration.

Methods: The association between digoxin use and mortality was assessed in 17,897 patients by using a propensity score-adjusted analysis and in new digoxin users during the trial versus propensity score-matched control participants. The authors investigated the independent association between serum digoxin concentration and mortality after multivariable adjustment.

Results: At baseline, 5,824 (32.5%) patients were receiving digoxin. Baseline digoxin use was not associated with an increased risk of death (adjusted hazard ratio [HR]: 1.09; 95% confidence interval [CI]: 0.96 to 1.23; p = 0.19). However, patients with a serum digoxin concentration ≥1.2 ng/ml had a 56% increased hazard of mortality (adjusted HR: 1.56; 95% CI: 1.20 to 2.04) compared with those not on digoxin. When analyzed as a continuous variable, serum digoxin concentration was associated with a 19% higher adjusted hazard of death for each 0.5-ng/ml increase (p = 0.0010); these results were similar for patients with and without heart failure. Compared with propensity score-matched control participants, the risk of death (adjusted HR: 1.78; 95% CI: 1.37 to 2.31) and sudden death (adjusted HR: 2.14; 95% CI: 1.11 to 4.12) was significantly higher in new digoxin users.

Conclusions: In patients with AF taking digoxin, the risk of death was independently related to serum digoxin concentration and was highest in patients with concentrations ≥1.2 ng/ml. Initiating digoxin was independently associated with higher mortality in patients with AF, regardless of heart failure.

Keywords: atrial fibrillation; digoxin; heart failure; mortality.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Anti-Arrhythmia Agents / administration & dosage
  • Anti-Arrhythmia Agents / adverse effects
  • Anti-Arrhythmia Agents / blood
  • Anti-Arrhythmia Agents / pharmacokinetics
  • Atrial Fibrillation* / diagnosis
  • Atrial Fibrillation* / drug therapy
  • Atrial Fibrillation* / mortality
  • Cause of Death*
  • Correlation of Data
  • Death, Sudden* / epidemiology
  • Death, Sudden* / etiology
  • Digoxin* / administration & dosage
  • Digoxin* / adverse effects
  • Digoxin* / blood
  • Digoxin* / pharmacokinetics
  • Female
  • Heart Failure* / diagnosis
  • Heart Failure* / mortality
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Risk Assessment / methods
  • Risk Assessment / statistics & numerical data
  • Risk Factors

Substances

  • Anti-Arrhythmia Agents
  • Digoxin