Digoxin therapy and associated clinical outcomes in the MADIT-CRT trial

Heart Rhythm. 2015 Sep;12(9):2010-7. doi: 10.1016/j.hrthm.2015.05.016. Epub 2015 May 27.


Background: Digoxin's pharmacological, hemodynamic, and electrophysiological properties are well understood. However, in modern heart failure (HF) treatment, its effect has yet to be fully investigated.

Objective: The aim of the present study was to determine the effects of digoxin on outcomes in patients with mild HF implanted with an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy with defibrillator (CRT-D) device.

Methods: We investigated the effect of digoxin treatment on the end points of HF/death, HF alone, death alone, and ventricular tachycardia or ventricular fibrillation (VT/VF) in 1820 patients with mild HF (New York Heart Association class I and II), prolonged QRS duration (≥130 ms), and reduced left ventricular ejection fraction (≤30%) enrolled in the Multicenter Automatic Defibrillator Implantation Trial - Cardiac Resynchronization Therapy trial. Multivariate Cox proportional hazards regression models were used to determine the effect of time-dependent digoxin usage on the end points.

Results: Digoxin therapy was not associated with an increased or decreased risk of HF/death (hazard ratio [HR] 1.07; 95% confidence interval [CI] 0.86-1.33; P = .0.56), HF alone (HR 1.1.04; 95% CI 0.82-1.32; P = .76), or death alone (HR 0.93; 95% CI 0.67-1.32; P = .71). However, digoxin was associated with a significant 41% increased risk of VT/VF (HR 1.41; 95% CI 1.14-1.75; P = .002), which was driven by a significantly increased risk of VT/VF with heart rate ≥200 beats/min (HR 1.65; 95% CI 1.27-2.15; P ≤ .001), whereas no increased risk of VT/VF with heart rate <200 beats/min was evident (HR 1.20; 95% CI 0.92-1.57; P = .19). No significant differences in digoxin's effect on any of the end points were found between patients with ICD and patients with CRT-D (interaction P > .5).

Conclusion: The use of digoxin in patients with mild HF implanted with an ICD or CRT-D device was not associated with reductions in HF/death events. However, digoxin therapy was associated with an increased risk of high-rate VT/VF (≥200 beats/min).

Keywords: CRT-D; Digoxin; Heart failure; ICD; MADIT-CRT; Mortality; Ventricular fibrillation; Ventricular tachyarrhythmia.

Publication types

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

MeSH terms

  • Canada / epidemiology
  • Cardiac Resynchronization Therapy / methods*
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / adverse effects
  • Digoxin / administration & dosage*
  • Digoxin / adverse effects
  • Dose-Response Relationship, Drug
  • Electrocardiography
  • Europe / epidemiology
  • Female
  • Follow-Up Studies
  • Heart Failure / physiopathology
  • Heart Failure / therapy*
  • Heart Rate / drug effects
  • Heart Rate / physiology
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Survival Rate / trends
  • Tachycardia, Ventricular / epidemiology*
  • Tachycardia, Ventricular / etiology
  • Tachycardia, Ventricular / physiopathology
  • Time Factors
  • United States / epidemiology


  • Cardiotonic Agents
  • Digoxin