Randomized, double-blind comparison of intravenous amiodarone and bretylium in the treatment of patients with recurrent, hemodynamically destabilizing ventricular tachycardia or fibrillation. The Intravenous Amiodarone Multicenter Investigators Group

Abstract

Background: After several days of loading, oral amiodarone, a class III antiarrhythmic, is highly effective in controlling ventricular tachyarrhythmias; however, the delay in onset of activity is not acceptable in patients with immediately life-threatening arrhythmias. Therefore, an intravenous form of therapy is advantageous. This study was designed to compare the safety and efficacy of a high and a low dose of intravenous amiodarone with bretylium, the only approved class III antiarrhythmic agent.

Methods and results: A total of 302 patients with refractory, hemodynamically destabilizing ventricular tachycardia or ventricular fibrillation were enrolled in this double-blind trial at 82 medical centers in the United States. They were randomly assigned to therapy with intravenous bretylium (4.7 g) or intravenous amiodarone administered in a high dose (1.8 g) or a low dose (0.2 g). The primary analysis, arrhythmia event rate during the first 48 hours of therapy, showed comparable efficacy between the bretylium group and the high-dose (1000 mg/24 h) amiodarone group that was greater than that of the low-dose (125 mg/24 h) amiodarone group. Similar results were obtained in the secondary analyses of time to first event and the proportion of patients requiring supplemental infusions. Overall mortality in the 48-hour double-blind period was 13.6% and was not significantly different among the three treatment groups. Significantly more patients treated with bretylium had hypotension compared with the two amiodarone groups. More patients remained on the 1000-mg amiodarone regimen than on the other regimens.

Conclusions: Bretylium and amiodarone appear to have comparable efficacies for the treatment of highly malignant ventricular arrhythmias. Bretylium use, however, may be limited by a high incidence of hypotension.