MADIT II

Cardiac Death Prevention — Trial Outcomes and Treatment Practices

There have been several landmark trials in cardiac death prevention in which the results have helped to change treatment practices. With its groundbreaking results, MADIT II may also effect a significant transition in the prevention of sudden cardiac death (SCD).

Study Descriptions

This is a noncomparative representation of trial outcomes that resulted in dramatic shifts in treatment practices.

COPERNICUS (Carvedilol Prospective Randomized Cumulative Survival Study)

Results of a multicenter, randomized, double-blind, placebo-controlled trial of the effect of the beta-blocker carvedilol on the survival of 2289 patients with severe heart failure and an ejection fraction (EF) <25%:

1133 patients were assigned placebo and 1156 carvedilol treatment for a mean period of 10.4 months.

There were 190 deaths in the placebo group and 130 deaths in the carvedilol group, reflecting a 35% reduction in the risk of death with carvedilol (95% confidence interval, 19% to 48%; P=0.0014, adjusted for interim analyses).1

SAVE (Survival and Ventricular Enlargement Trial)

Results of a multicenter, randomized, double-blind, placebo-controlled trial in 2231 patients with acute myocardial infarction and left-ventricular dysfunction (EF <40%):

1116 patients were assigned placebo and 1115 captopril treatment for an average of 42 months.

There were 275 deaths in the placebo group and 228 deaths in the captopril group, reflecting a 19% reduction in the risk of death with captopril (95% confidence interval, 3% to 32%; P=0.019).2

4S (Scandinavian Simvastatin Survival Study)

Results of a multicenter, randomized, double-blind, placebo-controlled trial in 4444 patients with coronary artery disease and total cholesterol 213 mg/dL to 309 mg/dL:

2223 patients were assigned placebo and 2221 simvastatin treatment for a mean period of 5.4 years.

There were 256 deaths in the placebo group and 182 deaths in the simvastatin group — relative risk of death of 0.70 (95% confidence interval, 0.58-0.85; P=0.0003), reflecting a 30% reduction in the risk of death with simvastatin.3

MADIT ll (Multicenter Automatic Defibrillator Implantation Trial ll)

Results of a multicenter, randomized trial in 1232 patients with prior myocardial infarction and a left-ventricular EF <30%:

490 patients were assigned conventional medical therapy only and 742 implantable cardioverter defibrillator (ICD) therapy for an average of 20 months.

There were 97 deaths in the conventional therapy group and 105 deaths in the ICD group — hazard ratio for death of 0.69 (95% confidence interval, 0.51-0.93; P=0.016) — reflecting a 31% reduction in the risk of death with ICD therapy.4

* COPERNICUS (Carvedilol Prospective Randomized Cumulative Survival Study)
† SAVE (Survival and Ventricular Enlargement Trial)
‡ 4S (Scandinavian Simvastatin Survival Study)
§ MADIT ll (Multicenter Automatic Defibrillator Implantation Trial ll)

References

Packer M, Coats AJS, Fowler MB, et al, for the Carvedilol Prospective Randomized Cumulative Survival Study Group. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001;344:1651-1658.
Pfeffer MA, Braunwald E, Moyé LA, et al, on behalf of the SAVE Investigators. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the survival and ventricular enlargement trial. N Engl J Med. 1992;327:669-677.
Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383-1389.
Moss AJ, Zareba W, Hall WJ, et al, for the Multicenter Automatic Defibrillator Implantation Trial II Investigators. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med. 2002;346:877-883.

Instructions for Use Summary

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