What was the early evidence for the efficacy of cardioverter-defibrillator (ICD) therapy?

Updated: Oct 11, 2019
  • Author: Daniel M Beyerbach, MD, PhD; Chief Editor: Jeffrey N Rottman, MD  more...
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Early data regarding the implantable cardioverter-defibrillator (ICD) was drawn primarily from uncontrolled series of patients for whom antiarrhythmic drug therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF) had failed. Even in these refractory patients, initial series suggested a markedly reduced risk of sudden, presumed arrhythmic, death. Subsequent randomized, controlled trials also focused on secondary prevention of sustained VT, VF, and sudden cardiac death. [8] In the early to-mid 1990s, three clinical trials were conducted in patients who had survived life-threatening ventricular tachyarrhythmias.

The Antiarrhythmics Versus Implantable Defibrillators (AVID) trial, conducted in the United States, enrolled patients with prior cardiac arrest or hemodynamically significant sustained VT and randomized patients to either ICD implantation or antiarrhythmic drug therapy, including primarily amiodarone and, in a few cases, sotalol. [9] The Canadian Implantable Defibrillator Study (CIDS) trial in Canada had a similar structure. [10, 11] The Cardiac Arrest Study Hamburg (CASH) trial in Hamburg enrolled cardiac arrest survivors and randomized them to amiodarone, metoprolol, propafenone, or ICD implantation. [12]

The AVID trial, although sponsored by the National Institutes of Health (NIH), was extremely controversial in its conception, because many electrophysiologists maintained that a randomized trial was not necessary to prove the effectiveness of the ICD. This trial was terminated prematurely because of improved survival rates in the ICD-treated patients. The CIDS trial yielded similar results. In the CASH trial, the propafenone arm of the study was terminated prematurely due to an increased mortality rate. [13] Ultimately, in the CASH trial, ICD therapy proved superior when compared with either amiodarone or metoprolol therapy.

These trials firmly established the ICD as preferred therapy in patients who have survived cardiac arrest or hemodynamically significant, sustained VT.

Subgroup analyses of results from the AVID trial, CIDS trial, and primary prevention Multicenter Automatic Defibrillator Implantation Trial (MADIT) [14] suggested that the survival benefit of the ICD is realized primarily by a well-defined subgroup of patients; specifically, those with greater impairment of left ventricular systolic function, as measured by left ventricular ejection fraction (LVEF), without end-stage (New York Heart Association [NYHA] class IV) heart failure. In these three trials, the ICD had less apparent benefit in patients with better-preserved left ventricular systolic function.

Several important trials have subsequently been performed examining the role of ICDs as primary therapy for patients who are at risk for but who have not yet manifested sustained ventricular arrhythmias. These trials include the MADIT (Multicenter Automatic Defibrillator Implantation Trial), MUSTT (Multicenter Unsustained Tachycardia Trial), MADIT II, SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial), and the COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Chronic Heart Failure) trial.

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