Sudden Cardiac Death in Heart Failure Trial - SCD-HeFT

Description:

The goal of the trial was to evaluate the effectiveness of amiodarone therapy or an implantable cardioverter defibrillator (ICD) with placebo in patients with New York Heart Association (NYHA) class II and III congestive heart failure (CHF) and reduced left ventricular ejection fraction (LVEF) ≤35%.

Hypothesis:

In patients with moderately symptomatic CHF and LVEF ≤35%, amiodarone and/or ICD added to standard medical therapy will be associated with reduced mortality compared with standard medical therapy alone.

Study Design

Study Design:

Patients Enrolled: 2,521
NYHA Class: 70% NYHA class II and 30% class III
Mean Follow Up: Median follow-up 45.5 months
Mean Patient Age: Median age 60 years
Female: 23
Mean Ejection Fraction: Baseline median EF 25%

Patient Populations:

1) 18 years of age or older.
2) Heart failure for at least three months and treated with a vasodilator.
3) Symptomatic CHF (NYHA class II and III) due to ischemic or nonischemic dilated cardiomyopathy.
4) LVEF ≤35% within three months of enrollment.
5) All patients are requested, but not required, to have had a coronary angiogram to document the nature of their disease. The definition of ischemic cardiomyopathy will be systolic LV dysfunction in the presence of ≤75% luminal coronary artery or insignificant coronary artery disease with definitive evidence of myocardial infarction (MI).
6) Patients with chronic atrial fibrillation must be anticoagulated with warfarin, with documented international normalized ratios of at least 2.0 for ≥21 days prior to randomization.

Exclusions:

1) Symptomatic ventricular arrhythmias.
2) LVEF >35% or asymptomatic LV dysfunction.
3) NYHA class IV CHF.
4) History of cardiac arrest or a spontaneous episode of sustained ventricular tachycardia (VT) (≥30 seconds at rates of >100 bpm) not associated with an acute Q-wave MI. (Sustained VT or an aborted cardiac arrest within 48 hours of an MI is not an exclusion criterion).
5) Any noncardiac disease that may cause death within 12 months.
6) Females who are pregnant or have childbearing potential and are not using reliable methods of contraception.
7) History of restrictive, infiltrative, or hypertrophic cardiomyopathy; constrictive pericarditis; acute myocarditis; congenital heart disease; surgically correctable valvular disease; and/or inoperable obstructive valvular disease.
8) History of mechanical prosthetic cardiac valves.
9) History of a major psychiatric disorder, active alcohol/drug abuse, or noncompliance.
10) Contraindication for taking amiodarone for any reason or currently taking amiodarone.
11) Indication for antiarrhythmic drugs.
12) Atrial fibrillation requiring catheter ablation of the atrioventricular conduction system or amiodarone for rate control.
13) Unexplained syncope within the last five years.
14) Patients unable to accommodate ICD placement in the left infraclavicular region.
15) Expected to undergo cardiac transplantation within 12 months.
16) Permanent pacemaker.
17) Liver function tests (>2.5 times normal or a serum creatinine >2.5 mg/dl).
18) Currently receiving antibiotics.

Primary Endpoints:

All-cause mortality

Secondary Endpoints:

1) Arrhythmic cardiac mortality.
2) Nonarrhythmic cardiac mortality.
3) Composite of all-cause mortality and rehospitalization for CHF.
4) Health-related quality of life.
5) Cost of care and calculate incremental cost-effectiveness ratios.

Drug/Procedures Used:

Patients were randomized in a double-blind manner to either: 1) Conventional CHF therapy and placebo, 2) conventional CHF therapy plus amiodarone, or 3) conventional CHF therapy plus a conservatively programmed single lead ICD. Amiodarone was dosed at 800 mg during the first week, 400 mg during weeks 2-4, and chronically at 200 mg/day if <150 lbs, 300 mg/day if 150-200 lbs, and 400 mg/day if >200 lbs.

ICDs were programmed for ventricular fibrillation (VF) treatment only. Patients underwent a six-minute walk test and Holter monitoring.

Principal Findings:

At the end of follow-up, medication use included 72% on angiotensin-converting enzyme inhibitors, 78% on beta-blockers, 80% on loop diuretics, and 55% on aspirin. Baseline median six-minute walk was 1,130 feet. Prior duration of CHF was 24.5 months at baseline.

There was no difference in all-cause mortality between the amiodarone and placebo arm (28% vs 29%, hazard ratio [HR] 1.06, 97.5% confidence interval [CI] 0.86-1.30, p=0.53), but mortality was lower in the ICD arm compared with placebo (22% vs 29%, HR 0.77, 97.5% CI 0.62-0.96, p=0.007). Subgroup analysis showed similar results for the amiodarone versus placebo comparison in the prespecified subgroups, with the exception of NYHA class III, which had an increased mortality in the amiodarone group (HR 1.44, 97.5% CI 1.05-1.97; n=497).

Interpretation:

Among patients with NYHA class II or III CHF and reduced LVEF, treatment with an implantable ICD was associated with a reduction in all-cause mortality compared with placebo, but there was no difference between amiodarone and placebo. The ICD was programmed for VF treatment only.

References:

Bardy GH, et al. Amiodarone or an Implantable Cardioverter-Defibrillator for Congestive Heart Failure. N Engl J Med 2005;352:225-37.

Presented by Dr. Gust H. Bardy at the American College of Cardiology Annual Scientific Session, March 2004.

Bardy GH, Lee KL, Mauk DB, and the SCD-HeFT Pilot Investigators. The Sudden Cardiac Death in Heart Failure Trial: pilot study. PACE 1997;20:1148 (Abstract).

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Atherosclerotic Disease (CAD/PAD), Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure

Keywords: Early Intervention (Education), Coronary Artery Disease, Myocardial Infarction, Follow-Up Studies, Ventricular Fibrillation, Sodium Potassium Chloride Symporter Inhibitors, Vasodilator Agents, International Normalized Ratio, Heart Failure, Stroke Volume, Electrocardiography, Ambulatory, Confidence Intervals, Ventricular Dysfunction, Left, Death, Sudden, Cardiac, Cardiomyopathy, Dilated, Defibrillators, Implantable


< Back to Listings