A placebo-controlled study to determine the efficacy of oral disopyramide phosphate for the prophylaxis of ventricular dysrhythmias after acute myocardial infarction.

1 To evaluate oral disopyramide phosphate in the prophylaxis of dysrhythmias occurring in acute myocardial infarction (MI) patients (presenting within 12 h of symptoms, age 21-70 years), a placebo-controlled, randomized double-blind, in hospital trial was conducted. After prognostic stratification (anterior and non-anterior MI at each of 4 regional hospitals) patients were randomly assigned to receive oral disopyramide phosphate (loading dose 150, 200, or 300 mg followed 6 h later by 100, 150, or 200 mg every 6 h for patients assessed to weigh less than 55, 55-85, or greater than 85 kg, respectively or matching placebo. The primary exclusion criteria were overt heart failure, systolic BP less than 100 mmHg, significant heart block or history of urinary retention. Active drug or placebo was continued for 7 days or until (a) detection of "warning arrhythmias' requiring i.v. lignocaine intervention (greater than 5 for 7 days or until (a) detection of "warning arrhythmias' requiring i.v. lignocaine intervention (greater than 5 premature ventricular contractions (PVCs)/min, R on T PVCs, multifocal PVCs, bigeminal PVCs, ventricular tachycardia or ventricular fibrillation) or (b) onset of exclusion criteria. In addition, plasma drug concentrations were determined and 24 h electrocardiographic tapes were obtained on day 1, and on one of days 4-7 but these results are not presented here. 2 Out of 121 patients entering the trial, 101 had confirmatory ECG and enzyme changes. Of these, 9 of 47 patients receiving disopyramide phosphate required lignocaine compared to 20 of 54 receiving placebo (19% v 37%; P = 0.047). Corresponding numbers for patients discontinuing trial medication for other non-fatal complications of MI were 5 and 3, and for those dying, were 3 (2 infarct extensions and 1 massive infarction), and 0, respectively. Respective numbers discontinuing trial medication for possible drug side effects (viz. urinary retention requiring catheterization) were 6 and 1 (P = 0.031). 3 In circumstances where i.v. therapy is deemed impractical, use of oral disopyramide phosphate given prophylactically in patients with acute MI may reduce the incidence of "warning arrhythmias' by a clinically significant extent.

RCT Entities:   Population Interventions Outcomes