Long-term efficacy of oral pirmenol in suppressing ventricular premature depolarizations.
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 suppressing 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 less than 30 VPDs/hr, greater than 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 (greater than 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 failed 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.(ABSTRACT TRUNCATED AT 250 WORDS)
de Buitleir
M
M
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0022.
Crevey
B J
BJ
Johnson
T
T
Kou
W H
WH
Nelson
S D
SD
Schmaltz
S
S
Morady
F
F
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D005117:Cardiac Complexes, Premature / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D006352:Heart Ventricles; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D011897:Random Allocation; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; C024318:pirmenol