title: Digoxin therapy and associated clinical outcomes in the MADIT-CRT trial.
abstract: 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).
  
  
  CONCLUSIONS
  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).
authors.affiliation: Heart Research Follow-Up Program, University of Rochester Medical Center, Rochester, New York.
authors.forename: Andy Y
authors.initials: AY
authors.lastname: Lee
authors.affiliation: Heart Research Follow-Up Program, University of Rochester Medical Center, Rochester, New York.
authors.forename: Valentina
authors.initials: V
authors.lastname: Kutyifa
authors.affiliation: Heart Research Follow-Up Program, University of Rochester Medical Center, Rochester, New York; Department of Cardiology, Gentofte University Hospital, Hellerup, Denmark.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Ruwald
authors.affiliation: Heart Research Follow-Up Program, University of Rochester Medical Center, Rochester, New York.
authors.forename: Scott
authors.initials: S
authors.lastname: McNitt
authors.affiliation: Heart Research Follow-Up Program, University of Rochester Medical Center, Rochester, New York.
authors.forename: Bronislava
authors.initials: B
authors.lastname: Polonsky
authors.affiliation: Heart Research Follow-Up Program, University of Rochester Medical Center, Rochester, New York.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
authors.affiliation: Heart Research Follow-Up Program, University of Rochester Medical Center, Rochester, New York. Electronic address: heartajm@heart.rochester.edu.
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
authors.affiliation: Heart Research Follow-Up Program, University of Rochester Medical Center, Rochester, New York; Department of Cardiology, Gentofte University Hospital, Hellerup, Denmark.
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Ruwald
mesh_terms: D002170:Canada / Q000453:epidemiology; D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000009:adverse effects; D004077:Digoxin / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D017180:Tachycardia, Ventricular / Q000453:epidemiology* / Q000209:etiology / Q000503:physiopathology; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: D002316:Cardiotonic Agents; D004077:Digoxin
keywords: CRT-D; Digoxin; Heart failure; ICD; MADIT-CRT; Mortality; Ventricular fibrillation; Ventricular tachyarrhythmia