June 15, 1996
View Full PaperEffect of Amiodarone on Clinical Status and Left Ventricular Function in Patients With Congestive Heart Failure
Key Result
Amiodarone increased left ventricular ejection fraction but did not significantly reduce heart failure hospitalizations compared to placebo (11.1% vs 13.6%; RR 0.81; 95% CI 0.56-1.10; P=0.18).
Study Design
Type
RCT (n=674)
Blinding
double-blind
Randomization
randomized
Multicenter
Yes
Structured PICO
Does amiodarone improve clinical status, left ventricular function, or reduce hospitalizations in patients with congestive heart failure and LVEF ≤ 40%?
P
Population
674 patients with congestive heart failure, New York Heart Association class II through IV symptoms, and left ventricular ejection fraction ≤ 40%
I
Intervention
Amiodarone
C
Comparator
Placebo
O
Outcome
Change in left ventricular ejection fraction, improvement in symptoms and/or physical findings of heart failure, and number of hospitalizations for heart failure
Amiodarone increases left ventricular ejection fraction in patients with congestive heart failure but does not provide overall clinical benefit, though it may reduce hospitalizations and cardiac death in patients with nonischemic etiology.
Main Result
Effect estimate: RR 0.81 (95% CI 0.56 to 1.10)
Absolute Event Rate: 11.1% vs 13.6%
p-value: p=.18
Abstract
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 < or = 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.