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)