Title of Trial
MADIT II (Multicenter Automatic Defibrillator Implantation Trial II)

Date and location of presentation
ACC 2002

Date and citation of primary publication(s) or References
New England Journal of Medicine 2002;346:877-83

Purpose of the Trial
In 1996 MADIT I demonstrated that the implantation of an ICD improved survival in patients with CAD, a reduced LVEF, NSVT, and inducible VT. MADIT II was designed to see if patients with a prior MI and advanced LV dysfunction would receive survival benefit from prophylactic ICD implantation without undergoing EPS for risk stratification.

Study Categories
ICD, Ventricular arrhythmias/Sudden Death

Patient Population
Patients with a prior myocardial infarction and severely reduced LVEF < 0.30

Inclusion Criteria
Age > 21 y.o. (no upper age limit); a history of an MI > 1 mo; LVEF < 0.30

Exclusion Criteria
FDA indication for an ICD; NYHA class IV; revascularization < 3 mos; h/o MI < 1 mo; advanced cerebrovascular disease; childbearing age without contraceptives; other illnesses with a high likelihood of death during the trial.

Study Design
Prospective, multicenter, randomized trial; 3:2 ratio to receive ICD + conventional medical therapy or conventional medical therapy alone; sequential design with preset stopping boundaries for efficacy, no difference, and inefficacy of ICD versus no ICD.

Primary Endpoint
Death from any cause

Secondary Endpoints
Usefulness of EPS during ICD implant to stratify risk; Quality of life & cost-effectiveness analysis; Determination of usefulness of non-invasive markers (e.g. SAECG, T-wave alternans, HRV, QT dispersion).

Baseline Characteristics
Number of patients: 1232 randomized patients (ICD: 742; Conventional: 490)
Mean Age: ICD=64 ± 10; Conv=65 ± 10
Gender: % female; 16% for ICD; 15% for Conv.
Other characteristics:
LEVF = 23 ± 5% (ICD); 23 ± 6% (Conv); NYHA I = 35% (ICD); 39% (Conv); NYHA II = 35% (ICD); 34% (Conv); NYHA = III 25% (ICD); 24% (Conv); NYHA IV = 5% (ICD); 4% (Conv); QRS > 120ms = 50% (ICD); 51% (Conv); amiodarone = 13% (ICD); 10% (Conv); beta-blocker = 70% (ICD); 70% (Conv); ACEI = 68% (ICD); 72% (Conv)

Years Follow-up: 20 months (6 days to 53 mos)

Results
The mortality rate was 19.8% in the conventional therapy group versus 14.2% in the ICD group. The hazard ratio for the risk of death from any cause in the ICD group, compared to the conventional therapy group, was 0.69 (p=0.016). Subgroup analyses of QRS, LVEF, age, sex, and NYHA class showed similar survival benefit with ICD therapy.

Conclusion
In patients with a prior MI and advanced LV dysfunction, prophylactic ICD therapy improves survival when compared to conventional therapy alone.

Sponsor
Guidant

Trial Status: Completed

Review written by Sung Chun, M.D.