Digoxin use in contemporary heart failure with reduced ejection fraction: an analysis from the Swedish Heart Failure Registry

Eur Heart J Cardiovasc Pharmacother. 2022 Dec 2;8(8):756-767. doi: 10.1093/ehjcvp/pvab079.


Aims: Digoxin is included in some heart failure (HF) guidelines but controversy persists about the true role for and impact of treatment with this drug, particularly in the absence of atrial fibrillation (AF). The aim of this study was to assess the association between clinical characteristics and digoxin use and between digoxin use and mortality/morbidity in a large, contemporary cohort of patients with HF with reduced ejection fraction (HFrEF) stratified by history of AF.

Methods and results: Patients with HFrEF (EF < 40%) enrolled in the Swedish HF registry between 2005 and 2018 were analysed. The independent association between digoxin use and patient characteristics was assessed by logistic regression, and between digoxin use and outcomes [composite of all-cause mortality or HF hospitalization (HFH), all-cause mortality, and HFH] by Cox regressions in a 1:1 propensity score matched population. Digoxin use was analysed at baseline and as a time-dependent variable. Of 42 456 patients with HFrEF, 16% received digoxin, 29% in the AF group and 2.8% in the non-AF group. The main independent predictors of use were advanced HF, higher heart rate, history of AF, preserved renal function, and concomitant use of beta blockers. Digoxin use was associated with lower risk of all-cause death/HFH [hazard ratio (HR): 0.95; 95% confidence interval (CI): 0.91-0.99] in AF, but with higher risk in non-AF (HR: 1.24; 95% CI: 1.09-1.43). Consistent results were observed when digoxin use was analysed as a time-dependent variable.

Conclusion: The great majority of digoxin users had a history of AF. Digoxin use was associated with lower mortality/morbidity in patients with AF, but with higher mortality/morbidity in patients without AF.

Keywords: Digoxin; Heart failure with reduced ejection fraction; Hospitalization; Mortality; Registry; SwedeHF.

MeSH terms

  • Atrial Fibrillation* / diagnosis
  • Atrial Fibrillation* / drug therapy
  • Atrial Fibrillation* / epidemiology
  • Digoxin / adverse effects
  • Heart Failure* / diagnosis
  • Heart Failure* / drug therapy
  • Heart Failure* / epidemiology
  • Humans
  • Registries
  • Stroke Volume / physiology
  • Sweden / epidemiology


  • Digoxin