Amiodarone or a Implantable Cardioverter-Defibrilator for Congestive Heart Failure
Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005 20;352:225-37.
Ventricular arrhythmias are the leading cause of sudden cardiac death in patients with systolic heart failure. Treatment with antiarrhythmic drug therapy has failed to improve survival in these patients, due to their proarrhythmic effects. Unlike other antiarrhythmics, amiodarone is a drug with low proarrhythmic effects. Some studies have suggested that amiodarone may be beneficial in patients with systolic heart failure. Conversely, several primary and secondary prevention trials have demonstrated that placement of an implantable cardioverter-defibrillator (ICD) confers a survival benefit in patients with ischemic cardiomyopathy. However, the role of ICDs in nonischemic heart failure remained unproven.
Bardy and colleagues developed the Sudden Cardiac Death in Heart Failure Trial (SCDHeFT) to evaluate the hypothesis that treatment with amiodarone or a shock-only, single-lead ICD would decrease death from any cause in a population of patients with mild to moderate heart failure. They randomly assigned 2521 patients with New York Heart Association (NYHA) class II or II heart failure (and a led ventricular ejection fraction (LVEF) of 35% or less to conventional medical therapy plus placebo, conventional therapy plus treatment with amiodarone or conventional therapy plus a conservatively programmed, shock-only, single-lead ICD.
Fifty-two percent of patients had ischemic heart failure and 48% had nonischemic heart failure. Placebo and amiodarone were given in double-blind fashion. The primary endpoint was death from any cause with a median followup of 45.5 months. The results were as follows:
Placebo Group – 244 deaths (29% Death Rate)
Amiodarone Group – 240 deaths (28% Death Rate)
ICD Group – 182 deaths (22% Death Rate)
Patients treated with amiodarone had a similar risk of death as those who received placebo (hazard ratio, 1.06; 97.5% CI: 0.86–1.30; p=0.53). Patients implanted with an ICD had a 23% decreased risk of death when compared with those who received placebo (0.77; 97.5% CI: 0.62–0.96; p=.007). This resulted in an absolute risk reduction of 7.2% at 5 years. The authors concluded that in patients with NYHA class II or III heart failure and a LVEF of 35% or less, implantation of a single-lead, shock-only ICD reduced overall mortality by 23%, while treatment with amiodarone had no effect on survival. The benefit of ICD placement reached or approached significance in both the ischemic (hazard ratio .79, CI: 0.60–1.04, p= .05) and nonischemic (hazard ratio 0.73, CI: 0.50–1.07, p= 0.06) subgroups.
It is important to note that an additional subgroup analysis showed that ICD therapy had a significant survival benefit only in NYHA class II patients but not in NYHA class III patients. Amiodarone therapy had no benefit in class II patients and actually decreased survival in class III patients compared to those receiving placebo. In light of results from previous trials that demonstrated a greater survival benefit from ICD placement with worsening ejection fraction in patients with ischemic heart failure, the authors were unable to explain whether the differences in subclasses were biologically plausible.
This study is important for several reasons. First, it suggested that patients with systolic heart failure due to either ischemic or non ischemic causes would benefit from placement of an ICD. Second, these results support the conclusions of previous trials that demonstrate a survival advantage of ICD placement in patients with ischemic heart failure. Finally, this study also demonstrates that amiodarone therapy offers no survival benefit in this population of patients. (JL)