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Effect of amiodarone on clinical status and left ventricular function in patients with congestive heart failure.
B M Massie1, S G Fisher, M Radford
1Department of Veterans Affairs Cooperative Studies Program, Washington, DC, USA.
Insights
Amiodarone significantly increased left ventricular ejection fraction in heart failure patients, but did not improve symptoms or reduce hospitalizations overall. However, it showed a trend toward reducing cardiac death and hospitalizations in non-ischemic heart failure patients.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Amiodarone therapy in congestive heart failure (CHF) has shown mixed survival results.
- Studies indicate amiodarone increases left ventricular ejection fraction (LVEF) in CHF patients.
- The association between amiodarone-induced LVEF increase and clinical outcomes in CHF is unclear.
Purpose of the Study:
- To determine if amiodarone-induced LVEF increase in CHF patients correlates with symptom improvement.
- To assess if amiodarone therapy reduces hospitalizations for heart failure.
- To investigate the clinical benefits of amiodarone in CHF patients.
Main Methods:
- A randomized, double-blind, placebo-controlled trial involving 674 CHF patients (NYHA class II-IV, LVEF ≤40%).
- Patients received amiodarone or placebo for a median of 45 months.
- Clinical assessments and radionuclide LVEF measurements were taken at baseline and 6, 12, and 24 months.
Main Results:
- Amiodarone significantly increased LVEF compared to placebo at all time points (P < .001).
- No significant difference in clinical improvement, diuretic use, or heart failure hospitalizations between groups.
- A trend towards reduced combined cardiac death and hospitalizations was observed (P = .08).
Conclusions:
- Amiodarone substantially increases LVEF in CHF patients but lacks overall clinical benefit.
- A significant reduction in cardiac death plus hospitalizations was noted in the non-ischemic CHF subgroup (P = .01).
- Amiodarone may offer benefits for non-ischemic heart failure patients.
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.