Title of Trial
Multicenter Automatic Defibrillator Implantation Trial (MADIT)

Date and Citation of Primary Publication(s) or References
New England Journal of Medicine 1996;335:1933-40

Purpose of the Trial
Patients with prior MI, unsustained VT, and LV dysfunction have a potentially high mortality rate of up to 30% in two years. This study selected patients with a high risk for malignant ventricular arrhythmias within above patient group and tested whether a prophylactic ICD therapy would improve survival.

Study Categories
ICD, Ventricular arrhythmias/Sudden Death

Patient Population
Patients with prior MI, asymptomatic NSVT, and LVEF < 35% were screened.

Inclusion Criteria
Either sex; age 25-80 y.o.; h/o MI > 3 wks; asymptomatic NSVT (3-30 beats > 120bpm); LVEF < 35%; NYHA I, II, or III; no indication for revascularization as evaluated within 3 mos

Exclusion Criteria
H/o cardiac arrest or VT not associated with acute MI causing syncope or symptomatic hypotension; MI within 3 wks; CABG within 2 mos; PTCA within 3 mos; women of childbearing age w/o contraceptives; advanced cerebrovascular dz; non-cardiac dz associated w/ reduced likelihood of survival for the duration of the trial.

Study Design
Prospective, multicenter, randomized trial with two-sided sequential design; Eligible pts underwent EPS, and qualified for enrollment if sustained VT or VF was reproducibly induced and not suppressed after i.v. procainamide. These patients were randomized to either ICD therapy or conventional medical therapy alone. The decision as to whether to initiate therapy with an antiarrhythmic medication was left for an attending physician to decide for both groups.

Primary Endpoint
Death from any cause

Secondary Endpoints
Cardiac death

Baseline Characteristics
Number of patients: 196 patients ( ICD=95; Conv=101)
Mean Age: 64 ± 9 (Conv); 62 ± 9 (ICD)
Gender: % female; 8% (Conv); 8% (ICD)
Other characteristics:
NYHA II or III: 67% (Conv); 63% (ICD); LVEF: 25+7% (Conv); 27+7% (ICD); amiodarone: 74% (Conv); 2% (ICD); Beta-blocker: 8% (Conv); 26% (ICD); Class I AAD: 10% (Conv); 12% (ICD); no AAD: 8% (Conv); 56% (ICD); ACEI: 55% (Conv); 60% (ICD)

Years Follow-up: 27 months

Results
The study was terminated prematurely by the Safety & Monitoring Committee because the survival benfit noted with the ICD compared to conventional therapy.

There were 15 deaths (11 cardiac death) in the ICD group compared to 39 deaths (27 cardiac deaths) in the conventional medical therapy group. The hazard ratio for improvement in overall survival for the ICD arm compared to the conventional medical therapy arm was 0.46 (p=0.009). Subgroup analysis, including use of amiodarone, beta-blockers, or other antiarrhythmic agent use, did not demonstrate any significant influence on the hazard ratio.

Conclusion
In patients with a prior MI, asymptomatic NSVT, an LVEF < 35%, and inducible VT or VF that are not suppressible during EPS, a prophylactic ICD reduces mortality rates.

Sponsor
Guidant

Trial Status: Completed

Review written by Sung Chun, M.D.