Title of Trial
The Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation (DEFINITE)

Date and location of presentation:
November, 2003 AHA

Purpose of the Trial
Up to 1/3 of heart failure patients have non-ischemic cardiomyopathy as their etiology, yet there has not been a large-scale clinical trial to evaluate the role of ICD therapy in this patient population. DEFINITE is the first large-scale trial to present data concerning the potential benefit of ICD therapy in this patient population.

Study Category
ICD

Patient Population
Non-ischemic dilated cardiomyopathy

Inclusion Criteria
Non-ischemic dilated cardiomyopathy; spontaneous PVCs (> 10/hour or NSVT; LVEF <35%;

Exclusion Criteria
Symptomatic ventricular arrhythmia or history of sudden cardiac death; NYHA class IV heart failure

Study Design
Prospective, randomized trial to compare a "standard medical therapy" group (ACEI and Beta-blockers) with an "ICD" group (ACEI, Beta-blockers, and single-chamber ICD).

Primary Endpoints
All cause mortality

Secondary Endpoints
Sudden cardiac death rate

Baseline Characteristics

Number of patients: 458 patients from 45 centers in the US and Israel

Time to Follow-up
The average follow-up time was 82 days in the ON group, and 85 days in the OFF group (p=0.96).

Mean age:
58 years

Gender: % female; Unknown

Other characteristics: Mean EF of 21%

Years Follow-up: Mean of 26 + 4 months

Results:

Primary end-point
Overall 33 deaths were noted in the "standard medical therapy" group vs. 23 in "ICD" group (p=0.06). After 2 years, 13.8% mortality rate was seen in the "standard medical therapy" group vs. a 8.1% rate in the "ICD" group, representing respectively a 5.7% absolute reduction and a 34% relative risk reduction with ICD implantation. Subgroup analysis indicated that patients with NYHA Class III CHF had a highly significant decrease in all-cause mortality with ICD implantation (relative risk 0.34).

Secondary end-point
11 "arrhythmic deaths" were observed in the "Standard therapy" group vs. 3 in "ICD" group providing a hazard ratio of 0.26.

Conclusion
ICD therapy reduces the incidence of "arrhythmic death" in non-ischemic dilated cardiomyopathic patients with severe LV dysfunction and PVCs or NSVT concomitantly treated with ACEI and Beta-blockers. There was no statistically significant reduction in all-cause mortality noted between "standard therapy" group and "ICD" group.

Sponsor
St. Jude Medical

Trial Status: Completed

Review written by Sung Chun, M.D.