Dose-response range of encainide for benign and potentially lethal ventricular arrhythmias.
A multicenter, 2-week, double-blind, placebo-controlled, parallel group study was performed to determine the dose-response relation of encainide administered 3 times daily and to determine its onset of action. To be included in the study, patients with benign or potentially lethal ventricular arrhythmias were required to have an average of at least 30 ventricular premature complexes (VPCs) per hour on 48-hour Holter monitoring after a 48-hour washout period without antiarrhythmic drug treatment. Patients were randomly assigned to receive either placebo or 10, 25 or 50 mg of encainide 3 times daily (tid) for 2 weeks. Of the 125 patients who entered the study, 122 were available for efficacy analysis. Efficacy was determined using 24-hour Holter monitoring on days 1, 7 and 14. There was no difference in frequency of VPCs or of ventricular tachycardia events in the placebo and 10-mg-tid encainide arms. At doses of 25 and 50 mg of tid, encainide was effective in suppressing VPCs and in reducing the number of episodes of ventricular tachycardia. A positive dose-response relation was identified. The onset of effect of encainide was apparent at 3 hours and lasted for 24 hours with tid dosing. No difference in on-therapy conditions were found among the 4 study arms. No patients were discontinued from the study because of electrocardiographic changes. There was no statistically significant change in vital signs or physical examination data. In 1 patient an elevated serum glucose level developed. No symptomatic proarrhythmic events occurred and none required discontinuation of study medication.(ABSTRACT TRUNCATED AT 250 WORDS)
Morganroth
J
J
Pool
P
P
Miller
R
R
Hsu
P H
PH
Lee
I
I
Clark
D M
DM
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000813:Anilides / Q000627:therapeutic use*; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D016700:Encainide; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011897:Random Allocation; D013610:Tachycardia / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology
D000813:Anilides; D000889:Anti-Arrhythmia Agents; D016700:Encainide