Late-Breaking Trials from the American Heart Association Annual Scientific Sessions: DEFINITE
DEFINITE
Studies of selected patients with ischemic cardiomyopathy have shown improved survival with the use of prophylactic implantable cardioverter defibrillators (ICD). Thus, DEFibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) was designed to test the survival benefit of ICDs in patients with heart failure but without coronary artery disease.
Dr. Alan Kadish presented this study from 48 centers in the United States and Israel in which 458 patients were randomized to ICD or usual therapy. The entry criteria included left ventricular ejection fraction < 35%, class II or more symptoms at some point, and nonsustained ventricular tachycardia on telemetry or > 10 PVCs/hr on ambulatory ECG monitoring. These are similar to the MADIT study criteria in ischemic patients. Exclusion criteria included ventricular tachycardia (VT) > 15 beats at > 120 beats/min, amiodarone therapy for VT, or prior cardiac arrest. The study was stopped after 56 deaths by design. The ICD was set to fire at heart rates > 180 beats/min and provide back-up pacing. Baseline characteristics of the 2 groups were similar. Most were class II; 20% had left bundle branch block; 90% had VT; the mean LVEF was 21%; > 85% were on ACE inhibitors, beta blockers, and diuretics; and 42% were on digoxin.
The primary end point of total mortality was reduced by ICD at 2 years to 8% vs 14% on usual care, a 5.7% decline (P = .06), which did not meet the preset criteria for statistical significance (P = .05). The secondary end point of arrhythmic deaths was 3 patients on ICD vs 11 on usual care, which was statistically significant. No subgroup showed convincing benefit, but there was a trend toward more benefit in those with NYHA class III and those with lower LVEFs (< 20%). The investigators concluded that prophylactic ICD therapy in nonischemic dilated cardiomyopathy may be of value in selected patients, namely those with very low LVEF and more profound symptoms.
Comment by Michael H. Crawford, MD
The patients in this study were selected to mimic the MADIT-II criteria, which included a demonstrated propensity for ventricular arrhythmias. Yet, even with this selection, only arrhythmic deaths were prevented, not total deaths. Other studies have shown that arrhythmic deaths comprise only about half the deaths in these patients. There was a trend toward total mortality reduction in the sicker patients, but this was not significant. Other studies have shown that annual mortality in medically treated patients with dilated cardiomyopathy is about 6-7%. This is similar to the observed mortality on an ICD in this study but lower than the control mortality of 14% so this was a sicker patient population where larger differences might be expected. At this point, I would not recommend prophylactic ICD placement in all nonischemic dilated cardiomyopathy patients but would consider it in higher-risk patients with a demonstrated propensity to VT.
Dr. Crawford, Professor of Medicine and Associate Chief of Cardiology for Clinical Programs at the University of California, San Francisco, is Editor of Clinical Cardiology Alert.
Studies of selected patients with ischemic cardiomyopathy have shown improved survival with the use of prophylactic implantable cardioverter defibrillators (ICD). Thus, DEFibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) was designed to test the survival benefit of ICDs in patients with heart failure but without coronary artery disease.
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