Trial | Year | Number of patients enrolled (age in yrs.) | LVEF | Average follow up | Primary endpoint | Differentiate between Type II and Type III heart failure | Intervention | Findings |
MADIT-1 trial [29] | 1996 | 196 (25 - 80) | ・ LVEF ≤ 35% ・ NYHA class I-III | 27 months | Deaths from all cause | No | Conventional therapy (75% amiodarone ) vs. Conventional therapy combined with prophylactic ICD in 1:1 fashion | 54% reduction in total mortality in ICD arm. Improved survival with use of prophylactic ICD with conventional therapy. |
MUSTT trial [33] | 1999 | 704 (18 - 75) | ・ EF ≤ 40% | 39 months | Sudden cardiac death or cardiac arrest | No (75% of the patients had type I and II Heart failure) | Aggressive therapy (ICD or antiarrhythmic therapy) vs. Conventional therapy | 27% decrease in the risk of arrhythmic death or cardiac arrest in ICD arm. HR for mortality benefit not significant (HR = 0.80) |
MADIT- II trial [30] | 2002 | 1232 (>21) | ・ EF ≤ 30% | 20 months | All-cause mortality | No | ICD vs. Conventional therapy (Beta-blockers, ACEI) in 3:2 fashion | 31% reduction in all-cause mortality in ICD arm (HR = 0.69) |
CAT trial [34] | 2002 | 104 (18 - 70) | ・ LVEF ≤ 30% ・ NYHA II-III | 22.8 months | All-cause mortality at 1 year | Yes (65% NYHA type II) | ICD arm vs. medical treatment arm | Non-significant difference in all-cause mortality between ICD and conventional therapy arm (p = 0.55) |
DINAMIT trial [35] | 2003 | 674 (18 - 80) | ・ LVEF ≤ 35% ・ NYHA I-III | 30 months | Mortality from any cause | No (61% NYHA type II) | Conventional therapy vs. Conventional therapy plus ICD in 1:1 ratio | Non-significant difference of overall mortality between the two arms. Increase in non-arrhythmic death in ICD arm. |
AMIOVIRT trial [36] | 2003 | 103 (≥18) | ・ LVEF ≤ 35% ・ NYHA I-III | 24 months | Total mortality | No (63% NYHA type II) | Amiodarone arm vs. ICD arm | Non-significant difference in all-cause mortality between the two arms (p = 0.8). Better arrhythmia free survival in non ICD arm. |
DEFINITE trial [37] | 2004 | 458 (20 - 84) | ・ LVEF ≤ 36% ・ NYHA class I-III | 29 months | All-cause mortality | No (57% NYHA type II Heart failure) | Conventional medical therapy for heart failure (amiodarone) vs. Conventional therapy plus ICD in 1:1 ratio | Non-significant reduction in all-cause mortality. Significant reduction in sudden death from arrhythmia (HR = 0.20; p = 0.006) Though not powered but a significant reduction in mortality in type III heart failure (HR = 0.37) |
SCD-HeFT trial [22] | 2005 | 2521 (≥18) | ・ LVEF ≤ 35% ・ NYHA class II-III | 45.5 months | All-cause mortality | Yes (70% NYHA II and 30% NYHA III) | Three arms [placebo, conventional therapy (amiodarone) and ICD arm] in 1:1:1 ratio | 23% reduction in all-cause mortality. Significant reduction in HR for NYHA II and non-significant for NYHA type III |
IRIS trial [38] | 2009 | 1311 (18 - 80) | ・ LVEF ≤ 40% ・ NYHA I-III | 37 months | Overall mortality | No (60% NYHA type II) | Early ICD vs. optimal medical therapy in 1:1 ratio | Non-significant difference of survival between ICD and medical therapy (p = 0.76) |