USEFULNESS OF SOTALOL FOR LIFE-THREATENING VENTRICULAR ARRHYTHMIAS

Two trial designs have been used in evaluating sotalol in patients with sustained tachyarrhythmias: open-label dose escalation and randomized comparison with reference agents. At least 7 open-label studies (n = 16-65) have been reported from single centers in patients in whom trials of numerous other antiarrhythmic agents were unsuccessful. At the doses used, usually 320-640 mg/day, plasma concentrations were in the range associated with both beta blockade and class III antiarrhythmic activity (2-3 mug/mL). These concentrations produced electrophysiologic changes that were consistent across studies: 10-16% increase in right ventricular effective refractory period (ERP), 4-8% increase in corrected QT interval (QT(c)), and 17-30% increase in sinus cycle length (corresponding to a 15-23% decrease in heart rate). In these open-label trials, sotalol suppressed inducible ventricular tachyarrhythmias in 20-72% of patients; the higher degrees of efficacy were reported when induction protocols were confined to double extrastimuli. Side effects leading to discontinuation of sotalol in patients with sustained ventricular tachycardia or fibrillation include fatigue (4.0%), marked bradycardia (3.0%), torsades de pointes (3.0%), and heart failure or pulmonary edema (1.00%). A multicenter randomized trial compared intravenous sotalol with intravenous procainamide in a double-blind prospective fashion. Sotalol suppressed ventricular tachyarrhythmias inducible with triple extrastimuli in 15 (30%) of 50 patients, whereas procainamide was effective in 10 (20%) of 50. In this and other series, responsiveness to sotalol was prospectively identified by a particularly fast tachycardia at baseline (e.g., cycle length of <270 msec), but not by the extent of changes in global indices of repolarization (QT(c), ERP). Several of these trials, at least 1 of which used implantable cardioverter/defibrillators as a backup, reported that initial suppression of inducible arrhythmias during sotalol therapy was predictive of a low incidence of arrhythmia recurrence during long-term treatment. These uncontrolled and controlled data indicate that, although side effects typical of combined class II and class III actions can occur during long-term therapy, sotalol appears to be at least as effective as, or slightly more effective than, currently available agents for the management of life-threatening ventricular arrhythmias.