PROSPECTIVE, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF LOW-DOSE AMIODARONE IN PATIENTS WITH SEVERE HEART-FAILURE AND ASYMPTOMATIC FREQUENT VENTRICULAR ECTOPY

Sudden cardiac death is a common cause of mortality in patients with congestive heart failure. To determine if low-dose amiodarone could reduce sudden death among these patients, a prospective, placebo-controlled, double-blind pilot trial was conducted. One hundred one patients with ejection fractions <30%, New York Heart Association class III or IV symptoms, and frequent but asymptomatic spontaneous ventricular ectopy (Lown class II to V) were randomly assigned to treatment with low-dose amiodarone (400 mg/day for 4 weeks and then 200 mg/day) or placebo. Mean follow-up was 357 days (range 4 to 1009 days). Side effects were infrequent and there was no difference in the incidence of side effects between the treatment groups. The frequency of spontaneous ventricular ectopy in the group receiving amiodarone fell from 4992 +/- 1240 beats/24 hours at baseline to 1135 +/- 494 beats/24 hours after 1 month of treatment (p = 0.02) and remained low after 6 months, while there was no change in ventricular ectopy among the patients receiving placebo. Despite the reduction in ectopy, there was no improvement in mortality or decrease in the incidence of sudden death. One-year mortality by Kaplan-Meier analysis was 28% in the group receiving amiodarone and 19% in the group receiving placebo (p = NS). One-year mortality in patients with > 75% reduction in ventricular ectopy after 1 month of treatment was 31% versus 17% in patients with less-than-or-equal-to 75% ectopic suppression (p = NS). Although the size of the trial and its statistical power do not eliminate the possibility of a significant reduction in mortality with low-dose amiodarone, any effect is likely to be modest, i.e., < 25%. Therefore low-dose amiodarone can be safely administered to patients with severely impaired myocardial function and will significantly suppress spontaneous ventricular ectopy. However, despite arrhythmia suppression, low-dose amiodarone may not reduce or may have only a modest effect on the incidence of sudden death in patients with heart failure and asymptomatic ventricular ectopy.