Analysis of mortality events in the Multicenter Automatic Defibrillator Implantation Trial (MADIT-II).

OBJECTIVES: The purpose of this study was to determine the efficacy of implantable cardiac defibrillator (ICD) therapy in preventing sudden cardiac death (SCD) in post-infarction patients with advanced left ventricular (LV) dysfunction.

BACKGROUND: The Multicenter Automatic Defibrillator Implantation Trial (MADIT-II) randomized 1,232 post-infarction patients with an ejection fraction of < or =30% to ICD or conventional therapy. In the ICD group, there was a 31% decrease in the risk of total mortality. However, a better understanding of the mode of death is desirable in order to refine therapeutic interventions in high-risk populations.

METHODS: We evaluated the 202 deaths, using a variation of the Hinkle-Thaler classification system as well as a clinical classification system to determine the incidence of SCD and the incidence of cardiac death due to progressive LV failure.

RESULTS: The SCD rates were 10.0% in the conventional group and 3.8% in the ICD group (p < 0.01). The hazard ratio for the risk of SCD in the ICD group compared with the conventional therapy group was 0.33 (95% confidence interval 0.20 to 0.53, p < 0.0001). The ICD had no meaningful effect on non-sudden death (p = 0.32). The effect of defibrillator therapy in reducing SCD was similar in subgroup analyses stratified according to relevant baseline characteristics.

CONCLUSIONS: The decrease in mortality with ICD therapy in MADIT-II is entirely due to a reduction in SCD, with similar reductions in SCD in a spectrum of subgroups stratified according to relevant baseline characteristics.