Multicenter Automatic Defibrillator Implantation Trial - MADIT

Description:

Investigators studied whether prophylactic therapy with an implanted cardioverter-defibrillator (ICD), as compared to pharmacotherapy, would improve survival in patients with coronary disease at high risk for ventricular arrhythmia.

Hypothesis:

An ICD is effective in preventing sudden cardiac death when compared with conventional therapy for those who are otherwise destined to die from primary ventricular fibrillation.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 196
NYHA Class: I - III
Mean Follow Up: 27 months
Mean Patient Age: 67
Female: Not given
Mean Ejection Fraction: Average = 26%

Patient Populations:

1) Men and women age 25-75 years who have had a previous Q-wave myocardial infarction (MI) (recent or old).
2) Nonsustained ventricular tachycardia.
3) The most recent enzyme-positive MI must have occurred more than one month previously.
4) Documented episode of nonsyncopal, nonsustained ventricular tachycardia (run of 3-30 ventricular ectopic beats at a rate >120 per minute).
5) Ejection fraction <0.35%.
6) New York Heart Association (NYHA) functional classes I-III.
7) Absence of an indication for coronary artery bypass surgery (CABG) on the basis of a cardiac evaluation within the past three months by exercise tolerance test, stress thallium study, or coronary angiography.
8) Must have undergone an electrophysiological study.
9) Electrophysiologic induction of ventricular tachycardia not suppressible with intravenous (IV) procainamide (or an equivalent IV antiarrhythmic agent) if the patient has had a previous reaction to procainamide.

Exclusions:

1) Previous cardiac arrest or syncopal ventricular tachycardia unassociated with an acute MI.
2) Cardiogenic shock, symptomatic hypotension while in stable baseline rhythm.
3) NYHA functional class IV.
4) CABG or coronary angioplasty within the past six months.
5) Enzyme-positive MI within the past month.
6) Radionuclide ejection fraction >0.35.
7) Those with angiographic evidence of coronary disease who are likely to undergo CABG.
8) Irreversible brain damage from pre-existing cerebral disease.
9) Women of childbearing potential not using medically prescribed contraceptive measures.
10) Presence of any disease other than the patient's cardiac disease associated with a reduced likelihood of survival for the duration of the trial (e.g., cancer, uremia, liver failure, etc.).
11) Participation in other clinical heart disease trials.
12) Unwillingness or inability to cooperate with the study.
13) Living at a distance from the clinic that would make travel difficult for follow-up visits.
14) Plans to move away from the area.
15) Unwillingness to sign a consent form.

Primary Endpoints:

Death from all causes

Drug/Procedures Used:

ICD or conventional drug therapy, which included amiodarone (74% of patients in the nondevice arm), digitalis, disopyramide, mexiletine, procainamide, tocainide, beta-blockers, and sotalol; few patients received type IA agents and no patients received type IC agents.

Principal Findings:

The Kaplan-Meier cumulative survival curve for the 196 patients after randomization showed improved survival in the ICD arm, with a separation that began early after implantation. This difference continued to the end of the trial. A log-rank statistic p value indicates that the likelihood of this benefit from the ICD by chance alone is <0.009.

The hazard ratio was 0.46. This means that there was a 54% reduction in total, all-cause mortality in the ICD arm relative to the best conventional treatment (p=0.009).

Most of the mortality reduction was caused by a decrease in arrhythmic death. Patients in the ICD group experienced arrhythmic death much less frequently than conventionally treated patients.

The average survival for the defibrillator group over a four-year period was 3.66 years compared with 2.80 years for conventionally treated patients. Accumulated net costs were $97,560 for the defibrillator group compared with $75,980 for individuals treated with medications alone. The resulting incremental cost-effectiveness ratio of $27,000 per life-year saved compares favorably with other cardiac interventions.

Interpretation:

The implantation of an ICD is associated with a significant 54% reduction in total mortality in high-risk coronary patients when compared with conventional medical therapy. An ICD is cost-effective in selected individuals at high risk for ventricular arrhythmias.

References:

1) Multicenter automatic defibrillator implantation trial (MADIT): design and clinical protocol. MADIT Executive Committee. Pacing Clin Electrophysiol 1991;14:920-27.
2) Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med 1996;335:1933-40.
3) Moss AJ. Update on MADIT: the Multicenter Automatic Defibrillator Implantation Trial. The long QT interval syndrome. Am J Cardiol 1997;79(6A):16-9.
4) Mushlin AI, Hall WJ, Zwanziger J, et al. The cost-effectiveness of automatic implantable cardiac defibrillators: results from MADIT. Multicenter Automatic Defibrillator Implantation Trial. Circulation 1998;97:2129-35.

Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Cardiac Surgery and Arrhythmias, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Exercise Tolerance, Procainamide, Myocardial Infarction, Tocainide, Ventricular Fibrillation, Tachycardia, Ventricular, Disopyramide, Coronary Angiography, Research Personnel, Thallium, Digitalis, Sotalol, Coronary Artery Bypass, Ventricular Premature Complexes, Defibrillators, Implantable, Death, Sudden, Cardiac, Mexiletine


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