DOSE-RANGING STUDY OF INTRAVENOUS AMIODARONE IN PATIENTS WITH LIFE-THREATENING VENTRICULAR TACHYARRHYTHMIAS

Background Oral amiodarone effectively suppresses ventricular arrhythm ias; however, full activity may take days or weeks. In patients with f requent, life-threatening ventricular arrhythmias, this delay is not a cceptable. Thus, in these patients, the speed and dosing accuracy of a n intravenous formulation would be beneficial. The goal of this study was to demonstrate the efficacy of intravenous amiodarone in patients with refractory, recurrent hemodynamically destabilizing ventricular t achycardia or ventricular fibrillation by determining a dose response among three regimens. Methods and Results A total of 342 patients were enrolled at 46 medical centers in the United States. Patients receive d one of three randomized, double-blind dose regimens delivering 125, 500, or 1000 mg during the first 24 hours. Supplemental infusions (150 mg) of intravenous amiodarone could be given to treat breakthrough ve ntricular arrhythmias. The key efficacy end points were the arrhythmia event rate, time to first arrhythmic event, and number of supplementa l infusions administered. The event rate decreased with increasing dos es: median values were 0.07, 0.04, and 0.02 events per hour for the 12 5-, 500-, and 1000-mg dose groups, respectively, representing a signif icant decrease from baseline event rates (P=.043), and approached sign ificance in the overall lest for trend (P=.067). There was a significa nt dose-related increase in the time to first event (trend test P=.025 ) and a significant dose-related decrease in the number of supplementa l boluses per hour (trend test P=.043). Hypotension was the most commo n (26%) treatment-emergent adverse event during intravenous amiodarone therapy; there was no dose-response relationship. Seventy-eight perce nt of the patients survived to at least 48 hours. Conclusions Intraven ous amiodarone is effective for the treatment of recurrent, life-threa tening ventricular tachyarrhythmias.