Long-term efficacy of oral pirmenol in suppressing ventricular premature depolarizations

Abstract

Pirmenol is an investigational type 1A antiarrhythmic drug the long-term efficacy of which has not been fully determined. Therefore the long-term efficacy of oral pirmenol in supprossing ventricular premature depolarizations (VPDs) was assessed in an open-label, dose-titration study. Twelve patients (eight men and four women; mean age 57 +/- 12 years) were treated for 24 to 36 months (mean 33 +/- 4). Seven had structural heart disease (three valvular heart disease, two ischemic heart disease, and two hypertensive heart disease) and five did not. The mean left ventricular ejection fraction was 0.63 +/- 0.13. Exclusion criteria included 15 beats of ventricular tachycardia (VT), or prior failure of more than two antiarrhythmic drugs. Drug efficacy was assessed by 24-hour ambulatory ECG monitoring performed every 3 months during the first year, every 4 months during the second year, and at 6-month intervals during the third year. The mean hourly frequency of VPDs during the placebo phase was 732 +/- 608. Seven patients (58%) were treated successfully with effective (>75%) long-term suppression of VPDs. Two patients (17%) had a partial response with effective suppression of VPDs for the first 16 months and 5 months of treatment, respectively. Three patients falled to show consistent suppression of VPDs while receiving pirmenol. The daily dose of pirmenol ranged from 200 to 500 mg (mean 317 +/- 94 mg at the beginning of the study and 375 +/- 97 mg at the end). No proarrhythmic effects were identified during long-term treatment, and none of the patients withdrew from the study prematurely. Mild side effects included dry mouth, bad taste, and urinary hesitancy. We conclude that oral pirmenol maintains effective long-term suppression of VPDs in approximately 60% of patients and is well tolerated during chronic administration. No proarrhythmic effects occurred during long-term treatment.