Efficacy and safety of d-sotalol, a pure class III antiarrhythmic compound, in patients with symptomatic complex ventricular ectopy. Results of a multicenter, randomized, double-blind, placebo-controlled dose-finding study. The d-Sotalol PVC Study Group.

BACKGROUND

There is increasing interest in pure class III antiarrhythmic compounds, ie, drugs in which the electrophysiological effect is confined to the propensity for producing an isolated lengthening of action potential duration. d-Sotalol represents the prototype of such pure class III agents. This double-blind, placebo-controlled, randomized dose-finding study evaluated the antiarrhythmic efficacy and safety of d-sotalol in patients with symptomatic chronic ventricular ectopy.

METHODS AND RESULTS

A total of 233 patients presenting with > or = 30 premature ventricular contractions (PVCs) per hour during drug-free Holter monitoring randomly received placebo or d-sotalol at dosages of 50, 100, or 200 mg BID. Drug efficacy was assessed by repeat Holter monitoring at the end of double-blind therapy. There was a dose-dependent increase in QT and QTc duration, indicating class III activity. A dose-related decrease in hourly PVC counts was observed, reaching statistical significance for patients receiving 200 mg d-sotalol BID (311 PVCs/h during baseline compared with 135 PVCs/h during active treatment, P < .05). Analysis of the primary efficacy criterion (ie, > or = 75% reduction in total PVCs/h) revealed a significant treatment effect only for the highest d-sotalol dose, with 8 patients (14%) meeting this criterion. Eighteen patients reported side effects, which led to drug discontinuation in 5. One sudden death and one nonfatal cardiac arrest occurred in patients with dilative cardiomyopathy receiving 200 mg d-sotalol BID. No incidence of torsade de pointes was reported.

CONCLUSIONS

d-Sotalol exerts dose-dependent class III activity in patients with symptomatic ventricular ectopy. Its PVC-suppressing activity is modest and becomes evident predominantly at dosages of 200 mg administered BID. The observation of drug-associated serious adverse arrhythmic events emphasizes the need for individualized careful dose titration, particularly in patients with advanced organic heart disease.