Impact of implantable cardioverter-defibrillator, amiodarone, and placebo on the mode of death in stable patients with heart failure: analysis from the sudden cardiac death in heart failure trial

Circulation. 2009 Dec 1;120(22):2170-6. doi: 10.1161/CIRCULATIONAHA.109.853689. Epub 2009 Nov 16.

Abstract

Background: The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) demonstrated that implantable cardioverter-defibrillator (ICD) therapy reduces all-cause mortality in patients with New York Heart Association class II/III heart failure and a left ventricular ejection fraction < or =35% on optimal medical therapy. Whether ICD therapy reduced sudden death caused by ventricular tachyarrhythmias without affecting heart failure deaths in this population is unknown.

Methods and results: SCD-HeFT randomized 2521 subjects to placebo, amiodarone, or shock-only, single-lead ICD therapy. Over a median follow-up of 45.5 months, a total of 666 deaths occurred, which were reviewed by an Events Committee and initially categorized as cardiac or noncardiac. Cardiac deaths were further adjudicated as resulting from sudden death presumed to be ventricular tachyarrhythmic, bradyarrhythmia, heart failure, or other cardiac causes. ICD therapy significantly reduced cardiac mortality compared with placebo (adjusted hazard ratio, 0.76; 95% confidence interval, 0.60 to 0.95) and tachyarrhythmia mortality (adjusted hazard ratio, 0.40; 95% confidence interval, 0.27 to 0.59) and had no impact on mortality resulting from heart failure or noncardiac causes. The cardiac and tachyarrhythmia mortality reductions were evident in subjects with New York Heart Association class II but not in subjects with class III heart failure. The reduction in tachyarrhythmia mortality with ICD therapy was similar in subjects with ischemic and nonischemic disease. Compared with placebo, amiodarone had no significant effect on any mode of death.

Conclusions: ICD therapy reduced cardiac mortality and sudden death presumed to be ventricular tachyarrhythmic in SCD-HeFT and had no effect on heart failure mortality. Amiodarone had no effect on all-cause mortality or its cause-specific components, except an increase in non-cardiac mortality in class III patients. [corrected]

Clinical trial registration information: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000609.

Publication types

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

MeSH terms

  • Amiodarone / therapeutic use*
  • Anti-Arrhythmia Agents / therapeutic use*
  • Cause of Death
  • Combined Modality Therapy
  • Death, Sudden, Cardiac / epidemiology
  • Death, Sudden, Cardiac / prevention & control*
  • Defibrillators, Implantable*
  • Follow-Up Studies
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Humans
  • Kaplan-Meier Estimate
  • Placebos
  • Proportional Hazards Models
  • Risk Factors
  • Tachycardia / drug therapy*
  • Tachycardia / mortality

Substances

  • Anti-Arrhythmia Agents
  • Placebos
  • Amiodarone

Associated data

  • ClinicalTrials.gov/NCT00000609