Multicenter trial of sotalol for suppression of frequent, complex ventricular arrhythmias: A double-blind, randomized, placebo-controlled evaluation of two doses

• Published in: Journal of the American College of Cardiology Vol. 8; no. 4; pp. 752 - 762
• Main Authors: Anderson, Jeffrey L., Askins, Jack C., Gilbert, Edward M., Miller, Ronald H., Keefe, Deborah L., Somberg, John C., Freedman, Roger A., Haft, Lawrence R., Mason, Jay W., Lessem, Jan N.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.10.1986; Elsevier Science
• Subjects: Aged; Antiarythmic agents; Biological and medical sciences; Blood Pressure - drug effects; Cardiac Complexes, Premature - drug therapy; Cardiovascular system; Clinical Trials as Topic; Double-Blind Method; Electrocardiography; Female; Heart Rate - drug effects; Humans; Male; Medical sciences; Middle Aged; Monitoring, Physiologic; Pharmacology. Drug treatments; Random Allocation; Sotalol - administration & dosage; Sotalol - therapeutic use; Stroke Volume - drug effects; Heart; Human; Chemotherapy; Arrhythmia; Multicenter study; Placebo; Double blind study; Cardiovascular disease; Posology; Antiarrhythmia agent; Excitability disorder; Beta blocking agent
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/S0735-1097(86)80414-4

Sotalol is a unique beta-adrenergic blocking agent with additional actions characteristic of Vaughn-Williams class III antiarrhythmic agents in experimental models. To test the efficacy of Sotalol to suppress ventricular arrhythmias, a 6 week parallel, placebo-controlled outpatient study of two doses (320 and 640 mg/day, in two divided doses) was performed in four hospitals in 56 patients with chronic premature ventricular complexes at a frequency of 30/h or more (mean ± SE, 528 ± 60/h) on 48 hour ambulatory electrocardiographic recording. During a placebo week, no change occurred in arrhythmia frequency (532 ± 76/h). Subsequent Sotalol therapy significantly reduced median arrhythmia frequency in patients receiving both low (n = 19) and high (n = 18) doses compared with that in patients receiving placebo (by 77 and 83%, respectively, versus 6%; p < 0.001). Twenty-two (59%) of 37 sotalol-treated patients, 11 in each group, reached the prospectively defined criterion of efficacy (≥75% arrhythmia reduction) versus 2 (11%) of 19 placebo control patients (p < 0.001). Sotalol reduced the median frequency of couplets by 94% (p < 0.0001) and that of runs by 89% (p < 0.0007). The electrocardiographic effects of Sotalol included reductions in heart rate (by 17 to 27%) and increases in the QTc (by 6 to 9%) and PR (by 6%) intervals. Ejection fraction was unchanged. The most common adverse side effect was fatigue, but drug discontinuation was required in only three patients taking 640 mg/day. No proar-rhythmic events or biochemical abnormalities were observed. In summary, Sotalol displays significant antiarrhythmic activity of moderately high degree with good tolerance in doses of both 320 and 640 mg/day. Its antiarrhythmic actions are distinguished from those reported for other beta-blockers by its effects on the QTc interval and its moderately high degree of antiarrhythmic activity.