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Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation - DEFINITE
Description:
The goal of the trial was to evaluate whether standard medical therapy plus an implantable cardioverter defibrillator (ICD) will be associated with improvements in survival compared with standard medical therapy alone in patients with nonischemic dilated cardiomyopathy, ejection fraction (EF) ≤35%, and spontaneous premature ventricular complexes or nonsustained ventricular tachycardia.
Hypothesis:
Treatment with standard medical therapy plus an ICD will be associated with improvements in survival compared with standard medical therapy alone in patients with nonischemic dilated cardiomyopathy, EF ≤35%, and spontaneous premature ventricular complexes or nonsustained ventricular tachycardia.
Study Design
Study Design:
Patients Enrolled: 458
NYHA Class: NYHA class III in 21% of patients
Mean Follow Up: Mean 26 months
Mean Patient Age: Mean age 58 years
Female: 71
Mean Ejection Fraction: Mean baseline EF 21%
Patient Populations:
Age 21-80 years, nonischemic dilated cardiomyopathy, symptomatic congestive heart failure (CHF) with left ventricular (LV) ejection fraction ≤35%, and either nonsustained ventricular tachycardia or an average of 10 premature ventricular contractions (PVCs) per hour on 24-hour Holter
Exclusions:
Coronary artery disease, arrest, history of sustained ventricular tachycardia or ventricular fibrillation, NYHA class IV CHF, permanent pacemaker, or amiodarone use for treatment of ventricular arrhythmias
Primary Endpoints:
All cause-mortality
Secondary Endpoints:
Sudden cardiac death, quality of life, and cost-effectiveness
Drug/Procedures Used:
Patients were randomized to standard medical therapy plus implantation of a single chamber ICD (n=229) or standard medical therapy alone (n=229). Standard medical therapy included angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and when needed digoxins and diuretics. ICD was programmed VVI 40 bpm, VF zone only; 180 bpm.
Principal Findings:
Most patients were treated with ACE inhibitors (86%) and beta-blockers (85%). Baseline characteristics were similar in both treatment arms, with the exception of time from cardiomyopathy diagnosis, which was longer in the standard medical therapy arm (3.3 years vs. 2.4 years, p=0.04). The primary endpoint of all-cause mortality at two years was 13.8% in the standard medical therapy arm and 8.1% in the ICD arm (hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.40-1.06; p=0.08).
While the difference in all-cause mortality did not reach statistical significance, there was a significant reduction in sudden cardiac death in the ICD arm (n=3 vs. n=14; HR 0.20, 95% CI 0.060-0.71; p=0.006). In the subgroup of patients with New York Heart Association (NYHA) class III, all-cause mortality was signficantly lower in the ICD arm (HR 0.37, 95% CI 0.15-0.90; p=0.02).
Interpretation:
Among patients with nonischemic dilated cardiomyopathy, EF ≤35%, and spontaneous premature ventricular complexes or nonsustained ventricular tachycardia, treatment with standard medical therapy plus single chamber ICD implantation was associated with a nonsignificant reduction in all-cause mortality.
The present study is the first randomized trial of primary prevention therapy with ICDs in nonischemic cardiomyopathy patients. The MADIT II trial showed an improvement in mortality associated with ICD therapy in ischemic cardiomyopathy patients. A cost-effectiveness analysis will be performed.
References:
Kadish A, et al. Prophylactic Defibrillator Implantation in Patients with Nonischemic Dilated Cardiomyopathy. N Engl J Med 2004;350:2151-8.
Presented by Dr. Alan Kadish at the November 2003 American Heart Association Annual Scientific Sessions, Orlando, FL.
Keywords: Tachycardia, Ventricular, Digoxin, Diuretics, Heart Failure, Confidence Intervals, Ventricular Premature Complexes, Death, Sudden, Cardiac, Defibrillators, Implantable, Cardiomyopathy, Dilated
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