Primary prevention of sudden cardiac death with implantable cardioverter defibrillators: lessons learned from MADIT and MUSTT.

Abstract

The MADIT study lead to the first approved prophylactic indication for ICDs in patients with previous myocardial infarction, depressed left ventricular systolic function, nonsustained ventricular tachycardia (VT), and inducible sustained VT. However, criticisms have been raised with respect to the study design and patient selection. The MUSTT yielded similar results (51% lower mortality by ICD vs no antiarrhythmic drugs) in a comparable population. The results of MUSTT address the major criticisms of MADIT: (1) MADIT was a "small" study (n = 196), while MUSTT randomized 704 patients. (2) MADIT had an "imbalance" in its prescription of beta-blockers, whereas the "imbalance" favored the control group in MUSTT: (51% vs 34%). (3) MADIT had no untreated limb, but MUSTT did. (4) MADIT's control group mortality (32% at 2 years) was considered by some as "unrealistically high", yet MUSTT measured a similar rate (28% at 2 years). (5) MADIT presented no information relative to patients without inducible arrhythmias, but MUSTT recorded their outcomes in a registry. In conclusion, the combined results of MADIT and MUSTT confirm the appropriateness of their risk stratification schemes and the survival benefits of ICD therapy as a highly effective primary prevention in this high risk population.