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| TITLE |
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Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure
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| AUTHORS |
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Gust H Bardy, Kerry L Lee, Daniel B Mark, Jeanne E Poole, Douglas L Packer, Robin Boineau, Michael J. Domanski, Charles Troutman, Jill Anderson, George Johnson, Steven E McNulty, Nancy Clapp-Channing, Linda D Davidson-Ray, Elizabeth S Fraulo, Daniel P Fishbein, Richard M Luceri, John H Ip, The SCD-HeFT Investigators
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| PUBLICATION INFORMATION |
Journal Name: The New England Journal of Medicine
Volume: 352(3)
Pages: 225-37
Date Published: 01/20/2005
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| ABSTRACT/REVIEW |
What were the researchers trying to learn in this study?
The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) was designed to compare the benefits of treating patients with mild to moderate heart failure with either a medication or with an implanted defibrillator. Specifically, they compared the survival of these patients treated with the drug amiodarone to patients treated with a single-lead, implanted cardioverter defibrillator, or ICD.
Amiodarone (am-ee-OH-da-rone) belongs to a group of antiarrhythmic drugs that affect the activity of the heart by causing a delay in how fast the heart is ready to respond to another electrical impulse. It is marketed under the brand name, Cordarone®.
The ICD device used in this study was a shock-only, single-lead device manufactured by Medtronic (model 7223). The ICD was programmed to only treat rapid or chaotic beating of the lower heart chambers (sustained ventricular tachycardia or ventricular fibrillation).
What did they find?
The study had two main findings. First, therapy with a conservatively programmed, shock-only ICD significantly decreased the risk of death by 23% relative to patients taking a sugar pill (placebo). The absolute reduction in the risk of dying was 7.2% at five years among patients with heart failure who also received beta-blockers, angiotensin converting enzyme inhibitors, and other current standard heart disease treatments. This benefit remained the same regardless of the initial cause of heart failure, but did vary according to the New York Heart Association (NYHA) class. The second significant finding was that amiodarone had no beneficial effect on survival, despite the appropriate use of the medication and satisfactory continuation rates over longer periods than in other placebo-controlled trials.
After a median follow-up of 45.5 months, there were 244 deaths in the placebo group (29%), 240 deaths in the amiodarone group (28%), and 182 deaths in the ICD group (22%).
By the end of the study period, the only complications the participants treated with amiodarone had more frequently than the participants who had been treated with the placebo were more tremor (4%) and lowered functioning of the thyroid (hypothyroidism), occurring in 6% of the amiodarone group.
For the ICD group, implantation was unsuccessful in 1 patient (less than 1%). Also, 32 patients (4%) had their ICDs removed during the study period. ICD complications requiring surgery, hospitalization, or unexpected drug therapy occurred in 5% of the patients when the device was placed and in 9% of the patients during the follow-up period. During the trial, 259 patients (31%) received an ICD shock, of which 177 patients (68% of those receiving a shock) received a shock for serious rhythm disturbances (ventricular tachycardia or ventricular fibrillation).
Some patients in each group "crossed over" to the other treatment; 113 patients in the ICD group (14%) took amiodarone for at least some period of time and 188 patients in the amiodarone group (11%) received an ICD during the study.
Who was studied?
A total of 2,521 patients with mild to moderate heart failure were included. Patients needed to be at least 18 years old and have a New York Heart Association II or III functional status. Roughly half of the patients studied were between ages 51 and 69. Patients could have no greater than a 35% ejection fraction, and the median left ventricular ejection fraction (LVEF) was 25%. The ejection fraction is a measure of the amount of blood pumped out of the lower heart chambers (ventricles) with each contraction of the heart muscle. The cause of chronic heart failure was damage to the heart muscle due to lack of blood flow (ischemic) in 52% of the patients, and due to other causes (nonischemic) in 48%.
How was the study done?
From Sept. 16, 1997, to July 18, 2001, the researchers randomly assigned 2,521 patients in equal proportions to one of three groups (847 to placebo, 845 to amiodarone, and 829 to ICD therapy. The primary factor evaluated was death from any cause.
After a initial double dose of 800 mg of amiodarone given daily for one week, patients were given a maintenance dose of 400 mg daily for three weeks, followed by a dose of 200 to 400 mg daily based on weight.
The ICDs that were used had only one lead and were specifically programmed to deliver a shock for rapid or chaotic beating of the ventricles (sustained ventricular tachycardia or ventricular fibrillation). More sophisticated dual-chamber or bi-ventricular devices that monitor and/or pace the lower heart chambers separately were not permitted. The ICD was uniformly programmed to produce an electrical shock to the heart only when it detected a heart rate of 187 beats per minute or more.
Patients were followed every three months with alternating clinic visits and telephone calls. Data from the ICD memory log were regularly downloaded at these visits.
What did researchers know before starting this study?
Heart failure is a risk factor for sudden, unpredicted death from irregular heartbeats (arrhythmia) even with the appropriate use of proven medications such as beta-blockers. The use of amiodarone and the use of an implantable cardioverter-defibrillator (ICD) are two measures that have been developed specifically to prevent sudden death in people who have heart failure. Earlier clinical trials aimed at testing the ability of amiodarone to reduce the risk of death among patients with heart failure have not been conclusive.
The ability of an ICD to reduce deaths in patients with heart failure without a history of cardiac arrest has been evaluated in small trials focused on patients with weakened hearts not due to lack of blood flow (nonischemic cardiomyopathy). This approach in non-ischemic as well as ischemic heart failure also remains unproven.
Why did they do it?
Most of the survival data on amiodarone and ICD therapy have been obtained in clinical trials performed after heart attacks (myocardial infarction) in patients without heart failure or those with ventricular arrhythmias. This trial, called the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), was designed to evaluate whether amiodarone or a conservatively programmed shock-only, single-lead ICD would decrease the risk of death, regardless of the cause, in a large group of patients who had mild-to-moderate heart failure with a variety of characteristics.
What did the researchers say their study results mean?
The researchers concluded that in patients with NYHA class II or III heart failure who have a left ventricular ejection fraction of 35% or less, amiodarone does not improve survival, however, single-lead, shock-only ICD therapy reduces death by 23% compared to placebo.
They felt the results have the potential to improve care for many patients with heart failure. The trial confirmed findings of earlier trials that showed benefits of ICD therapy in patients with heart failure due to low blood flow (ischemia). It also showed increased survival when an ICD was used in patients who had heart failure from other causes. In this study, ICD therapy significantly benefited patients with NYHA class II heart failure, but did not benefit patients who had NYHA class III heart failure.
Amiodarone therapy, on the other hand, did not benefit patients who had NYHA class II heart failure, and actually decreased survival for patients who had NYHA class III heart failure.
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