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(Circulation. 1996;93:2128-2134.)
© 1996 American Heart Association, Inc.
Articles |
Effect of Amiodarone on Clinical Status and Left Ventricular Function in Patients With Congestive Heart Failure
From the Department of Veterans Affairs Cooperative Studies Program (S.G.F.), Washington, DC, and Hines, Ill; Veterans Affairs Medical Center and University of California (San Francisco) (B.M.M.); Veterans Affairs Medical Center, Fresno, Calif, and the University of California (San Francisco) (P.C.D.); Wadsworth Veterans Affairs Medical Center and the University of California (Los Angeles) (B.N.S.); and Veterans Affairs Medical Center and Georgetown University Medical School, Washington, DC (R.D.F., S.N.S.).
Correspondence to Barry M. Massie, MD, Cardiology Division (111C), VA Medical Center, 4150 Clement St, San Francisco, CA 94121.
Background Although trials of amiodarone therapy in patients with congestive heart failure have produced discordant results with regard to effects on survival, most studies have reported a significant rise in left ventricular ejection fraction during long-term therapy. In the present study, we determined whether this increase in ejection fraction is associated with an improvement in the symptoms and/or physical findings of heart failure or a reduction in the number of hospitalizations for heart failure.
Methods and Results In the Department of Veterans Affairs
cooperative study of amiodarone in congestive heart failure,
674 patients with New York Heart Association class II through IV
symptoms and ejection fractions of 
40% were treated with
amiodarone or placebo for a median of 45 months in a
randomized, double-blind, placebo-controlled protocol. Clinical
assessments and radionuclide ejection fraction were performed at
baseline and after 6, 12, and 24 months. Compared with the placebo
group, ejection fraction increased more in the amiodarone group
at each time point (8.1±10.2% [mean±SD] versus 2.6±7.9% at 6
months, 8.0±10.9% versus 2.7±8.0% at 12 months, and 8.8±10.1%
versus 1.9±9.4% after 24 months, all P<.001). However,
this difference was not associated with greater clinical improvement,
lesser diuretic requirements, or fewer hospitalizations for
heart failure (11.1% for amiodarone and 13.6% for placebo
group; overall relative risk in the amiodarone group, 0.81
[95% CI, 0.56 to 1.10], P=.18). Of note is the trend
toward a reduction in the combined end point of hospitalizations and
cardiac deaths (relative risk, 0.82 [CI, 0.65 to 1.03],
P=.08), which was significant in patients with
nonischemic etiology (relative risk, 0.56 [CI, 0.36 to
0.87], P=.01) and absent in the ischemic group
(relative risk, 0.95).
Conclusions Although amiodarone therapy resulted in a substantial increase in left ventricular ejection fraction in patients with congestive heart failure, this was not associated with clinical benefit in the population as a whole. The substantial reduction in the combined end point of cardiac death plus hospitalizations for heart failure in the nonischemic group suggests possible benefit in these patients.
Key Words: amiodarone • cardiomyopathy • heart failure • prognosis • morbidity
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