Proarrhythmic potential of moricizine: strengths and limitations of a data base analysis

Moricizine was studied in 908 patients with ventricular arrhythmias. A proarrhythmia occurred in 29 (3.2%). When the severity of the proarrhythmia and the type of presenting ventricular arrhythmia were correlated, no proarrhythmic events occurred in patients who presented with benign ventricular arrhythmias. Four deaths were attributed to the proarrhythmic effects of moricizine. Of these, 3 occurred in patients presenting with lethal ventricular arrhythmias. A total of 15 serious proarrhythmic events occurred, all of which resolved without lethal consequence. The overall proarrhythmia incidence in the lethal and potentially lethal ventricular arrhythmia categories was not different (3.2 vs 3.7%, respectively). Thus, a proarrhythmia occurred in patients with more advanced structural heart disease, and occurred almost exclusively in patients who presented with potentially lethal or lethal ventricular arrhythmia. There was no relation between the dose of moricizine and the incidence of proarrhythmic events. Of the 29 proarrhythmic events, 26 occurred within 7 days (90%) of the initiation of moricizine therapy. Thus, moricizine appears to have a low proarrhythmic potential in the populations tested, including patients presenting with lethal ventricular arrhythmias. The implications of the Cardiac Arrhythmia Suppression Trial on such a data base analysis are discussed.