In patients with HFrEF and NYHA II-III symptoms, how does amiodarone or ICD implantation compare to placebo in reducing mortality all-cause mortality?
SCD-HeFT demonstrated that ICDs reduced mortality compared to conventional therapy or amiodarone among patients with HFrEF.
Prophylactic ICD placement in post-MI patients with LVEF ≤30% was shown to improve survival in MADIT-II (2002). The role of ICDs and the antiarrhythmic amiodarone was unclear in those with heart failure with reduced EF regardless of MI history.
Single-lead, shock-only ICD therapy reduces mortality by 23% compared to conventional therapy or amiodarone in stable NYHA class II or III HF with EF <35%. Amiodarone conferred no survival benefit compared to placebo.
AHA/ACCF Heart Failure Guidelines (2013, adapted)
- ICD if nonischemic dilated cardiomyopathy or ICM ≥40 days post MI with LVEF ≤35% and NYHA class II or III symptoms on OMT with expected survival >1 year (class I, level A)
- ICD for ICM >40 days post MI with LVEF ≤30%, NYHA class I symptoms on OMT with expected survival >1 year (class I level B)
- Multicenter, double-blinded, parallel-group, randomized, placebo-controlled trial
- Amiodarone (n=845)
- Shock-only ICD (n=829)
- Placebo (n=847)
- Enrollment: 1997-2001
- Median follow up: 45.5 months
- Primary outcome: All-cause mortality
- Age >18 years
- NYHA class II-III chronic stable HF (ischemic or nonischemic)
- Median LVEF: 25%
- NYHA class II: 30%
- NYHA class III: 30%
- Ischemic CHF: 52%
- ACE inhibitor: 85%
- ACE inhibitor or ARB: 96%
- Beta-blocker: 69%
- Spironolactone: 19%
- Loop diuretics: 82%
- Aspirin: 56%
- Statin: 38%
- Randomized to ICD vs. amiodarone vs. placebo; all patients received conventional medical therapy as well
- All patients had EKG, 6-minute walk test, 24h Holter monitoring, LFTs, TFTs, and CXR
- All-cause mortality
- ICD vs. placebo
- 22% vs. 29% (HR 0.77; 97.5% CI 0.62-0.96; P=0.007)
- Amiodarone vs. placebo
- 28% vs. 29% (HR 1.06; 97.5% CI 0.86-1.30; P=0.53)
Funding from NHLBI, NIH, Medtronic, Wyeth–Ayerst Laboratories, and Knoll Pharmaceuticals.