Safety and efficacy of sotalol in patients with drug-refractory sustained ventricular tachyarrhythmias

Abstract

The safety and efficacy of oral sotalol, an investigational β-adrenergic blocker with class III antiarrhythmic drug properties, were examined in a multicenter study in 236 patients with sustained ventricular tachyarrhythmias. In 104 patients, the index arrhythmia was a cardiac arrest, and all patients had undergone at least 3 previous unsuccessful antiarrhythmic trials (mean = 5 per patient). In the 106 patients assessed by programmed electrical stimulation, sotalol completely suppressed induction of ventricular tachycardia (VT) in 33 (31%) and rendered VT slower (>100 ms prolongation of cycle length) or more difficult to induce in 29 (27%). Using continuous 24-hour ambulatory monitoring methods, sotalol complete- and partial-response rates were 51 and 12%, respectively. Of the 236 acute-phase patients, 151 were discharged receiving long-term sotalol therapy. The median sotalol dose was 480 mg/day. At a mean follow-up of 346 ± 92 days, 27 patients (18%) had recurrence of sustained arrhythmia; 9, sudden death; 11, sustained VT; 5, automatic defibrillator discharge; and 2, syncope. Adverse effects forced discontinuation of therapy in 10 patients (7%): 6 secondary to symptomatic bradyarrhythmia, 2 due to refractory heart failure, 1 due to torsades de pointes, and 1 from bronchospasm. Life-table analysis of sotalol's overall long-term efficacy at 6, 12 and 18 months were 80, 76 and 72%, respectively. Although mean follow-up was short (<1 year), neither acute-phase programmed stimulation nor 24-hour ambulatory monitoring responses were significantly predictive of subsequent arrhythmic outcome. Proarrhythmia was documented in 18 patients (7%), 17 during the acute phase and 1 during long-term follow-up. Proarrhythmia was manifested as torsades de pointes in 11 patients and as an increase in sustained VT episodes in 7. Of the 18 proarrhythmic complications, 14 (78%) occurred within 7 days of therapy. Symptomatic bradycardia occurred in 8 patients (3%) (7 during the acute phase, 1 long-term) and aggravation of heart failure in 7 (3%) (6 acute phase, 1 long-term). Thus, sotalol appears to be an effective agent for suppressing refractory, sustained ventricular tachyarrhythmias and is well tolerated during long-term therapy. Proarrhythmia was observed in 7% of patients and tended to occur during the acute titration phase. Accordingly, it is recommended that patients with sustained ventricular tachyarrhythmias treated with sotalol be observed under continuous electrocardiographic monitoring until acutephase dose titration has been completed.