Amiodarone in Heart Failure
Amiodarone in Heart Failure
ABSTRACT & COMMENTARY
Synopsis: Amiodarone is safe for treating patients with heart failure with a low incidence of pulmonary toxicity.
Source: Singh SN, et al. J Am Coll Cardiol 1997;30: 514-517.
Amiodarone has become increasing popular for the treatment of ventricular arrhythmias in patients with heart failure because of its superior efficacy compared to other antiarrhythmic drugs. Its use has increased due to the perception that low doses are associated with much lower toxicity. However, this hypothesis has not been fully tested. Thus, data from the Congestive Heart Failure-Survival Trial of Antiarrhythmic Therapy (CHF-STAT) study on the pulmonary toxicity of amiodarone is of interest. This was a prospective, randomized, placebo-controlled trial of amiodarone therapy in 674 patients with CHF; ejection fraction (EF) less than 40% on vasodilator therapy and more than 10 premature ventricular contractions (PVCs) per hour. Amiodarone was administered as 800 mg/day for 14 days, 400 mg/day for 50 weeks, then 300 mg/day. Pulmonary toxicity was assessed annually by chest x-ray and pulmonary function tests, including diffusing capacity of carbon monoxide (DLCO) in 519 patients. Follow-up ranged from 0 to 54 months (mean 45). Baseline characteristics were not different in the 250 placebo and 269 amiodarone patients; EF averaged 26%, and one-third of the patients had chronic obstructive pulmonary disease (COPD) by pulmonary function testing. DLCO measures did not differ between the two groups at baseline nor at follow-up, and there were no significant changes over time within each group or in the COPD subgroups. Survival free of non-cardiac death also was not different in the groups. Chest x-ray evidence of pulmonary fibrosis occurred in about 1% of patients and was not different between the groups. Singh and associates conclude that amiodarone is safe for treating patients with heart failure with a low incidence of pulmonary toxicity.
COMMENT BY MICHAEL H. CRAWFORD, MD
Physicians in other countries, especially in South America, have claimed for years that they have not observed the 5-10% pulmonary toxicity reported in the United States. They believe it is because they routinely used low doses (200-300 mg/day), and that these doses were efficacious. However, there were no blinded, randomized trials evaluating toxicity. The results of CHF-STAT seem to verify their position. Pulmonary complications, even in patients with COPD, were less than 3% and were not different in the control patients.
Only an analysis of patients alive at one year showed a significant change in DLCO over time in the amiodarone patients (-1.1 mL/min/mmHg) vs. controls (-0.04; P < 0.02). The decrease in COPD patients was also significant and larger (-2.1; P < 0.01). Since baseline DLCOs averaged 18 mL/min/mmHg, these changes were small.
Other types of pulmonary toxicity were slightly more frequent on amiodarone (6 patients vs 1), but the difference was not statistically different. Thus, considering the benefits of amiodarone, this degree of pulmonary toxicity seems acceptable. Other amiodarone adverse effects, such as thyroid abnormalities, were not mentioned in this report, but presumably they occurred. Before we unconditionally endorse low dose amiodarone for ventricular arrhythmias, it would be desirable to see all the toxicity data.
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