Authors
Bardy G, Lee K, Mark D, et al.
Title
Amiodarone or an Implantable Cardioverter-Defibrillator for Congestive Heart Failure
References
N Engl J Med 2005;352:225-37.
Background
Sudden cardiac death was common among patients with HF and systolic dysfunction. At the time of initiation of this study, the role of primary ICD therapy has not been well established in this patient population.
Purpose
To determine if single-shock ICD or amiodarone therapy increases survival rates in HF patients with mild-to-moderate symptoms (NYHA Class II or III) and low LVEF (≤0.35)
Design
  • Randomized, (double) blinded, placebo controlled trial
  • 2521 patients with NYHA class II or III symptoms, age ≥18 years, ejection fraction ≤35%, stable CHF (ischemic or nonischemic)
  • Permitted to receive standard treatment of ACE inhibitor and beta-blocker, and if appropriate, aldosterone antagonist, ASA, statin
Exclusion Criteria
  • n/a
Follow-Up
Median 45.4 months (24-72.6 months)
Treatment Regimen
  • randomized in 1:1:1 ratio to amiodarone vs. placebo vs. ICD
  • amiodarone 800 mg daily x 1 week, then 400 mg daily x 3 weeks, then maintenance dose of amiodarone based on weight vs. placebo (double blinded).
  • maintenance dose: if >90.0 kg, amiodarone 400 mg daily; 68.2-90.0 kg, amiodarone 300 mg daily; <68.2 kg, amiodarone 200 mg daily
  • ICD therapy (shock-only, single lead therapy)
Results

Primary Endpoints

Death from all causes:

  • 29% (placebo) vs. 28% (amiodarone); HR 1.06 (0.86-1.30), p=0.53
  • 29% (placebo) vs. 22% (ICD); HR 0.77 (0.62-0.96), p=0.007

Prespecified Subgroups

  • cause of CHF (ischemic or nonischemic) did not have a significant interaction with amiodarone (p=0.93) or ICD therapy (p=0.68)
  • NYHA classification had a significant interaction with amiodarone (p=0.004) and ICD therapy (p<0.001):
    • ICD vs. placebo:
      • NYHA class II - HR 0.54 (0.4-0.74), p<0.001
      • NYHA class III - HR 1.16 (0.84-1.61), p=0.30
    • Amiodarone vs. placebo:
      • NYHA class II – HR 0.85 (0.65-1.11), p=0.17
      • NYHA class III – HR 1.44 (1.05-1.97), p=0.010
Summary
Primary ICD shock therapy significantly increases survival rates in mild-to-moderate HF patients with low LVEF. Amiodarone provides no protective effect in this same patient population as compared to placebo.