Safety and efficacy of esmolol (ASL-8052: An ultrashort-acting beta-adrenergic blocking agent) for control of ventricular rate in supraventricular tachycardias

Abstract

Esmolol (ASL-8052) is a new intravenous beta-adrenergic blocking agent that has exhibited both cardiac selectivity and an extremely short half-life in animal studies. To assess its clinical efficacy, 16 patients were studied with a rapid ventricular rate associated with atrial flutter (n = 2), atrial fibrillation (n = 10), atrial tachycardia (n = 2) and multifocal atrial tachycardia (n = 2). During a 30 minute control period of observation, the ventricular rate ranged from 121 to 150 beats/min (mean 133.2 +/- 10.6). Using a double blind crossover method, esmolol was infused intravenously for a maximum of 60 minutes. Infusions of 50, 100, 150, 200, 250 and 300 micrograms/kg per min were given in consecutive 5 minute periods (during the first minute of each period, a loading dose of 500 micrograms/kg was given). Not all patients received the maximal dose. A response was defined as conversion to sinus rhythm or a 20% reduction in ventricular rate. One patient with atrial fibrillation associated with the Wolff-Parkinson-White syndrome did not respond. In the remaining 15 patients, their highest esmolol infusion rate was maintained for an additional 30 minutes. This resulted in a reduction in ventricular rate to a mean of 97.8 +/- 12.9 beats/min (range 72 to 119) (p less than 0.001). Conversion from flutter/fibrillation to sinus rhythm occurred in two patients. During the infusion, six had transient asymptomatic hypotension that was mild and manageable. After infusion, ventricular rate and blood pressure returned rapidly toward control values within 25 minutes in patients without conversion to sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)