754-4 Proven Efficacy of Repeated Dose Intravenous Ibutilide, a Class III Antiarrhythmic Drug, for Rapid Termination of Chronic Atrial Flutter or Fibrillation: Results of a Multicenter Placebo-Controlled Study

Abstract

Currently available antiarrhythmic drugs have limited efficacy for the acute, rapid, pharmacological termination of chronic atrial fibrillation (AF) or flutter (AFL). The objective of this double-blind, placebo-controlled, randomized, multicenter study was to determine the efficacy and safety of repeated doses of intravenous ibutilide in terminating AF and AFL. Two hundred forty-two evaluable patients (mean age 66.9 years, 80% male, 75% with heart disease) with sustained AF (n = 121) or AFL (n = 121) (duration 3 hrs to 45 days) were randomized into 3 groups to receive two 10-minute infusions separated by 10 minutes: placebo/placebo (n = 81); 1 mg/0.5 mg ibutilide (n = 79); 1 mg/l mg ibutilide (n = 82). The infusions were discontinued at the time of arrhythmia termination. The cumulative conversion efficacy after the two ibutilide infusions was greater (both p < 0.0001) than after placebo (47% vs. 2%). There was no significant difference in success rates between the two ibutilide doses (44% vs. 49%). Conversion efficacy of ibutilide was greater for AFL than AF (63% vs. 31%). In patients who failed to convert with the first infusion, the success rates after a second infusion were 2%, 27%, and 36% for placebo, 0.5 mg ibutilide and 1 mg ibutilide. The mean time to arrhythmia termination was 27 minutes after the start of the first infusion. Predictors of arrhythmia termination were arrhythmia duration and left atrial size (in AF group only). Ejection fraction, valvular disease, concomitant medications, plasma ibutilide concentration and QTc interval did not predict arrhythmia termination. Of 180 total ibutilide patients, 3 (1.7%) developed sustained polymorphic ventricular tachycardia (PVT) requiring cardioversion and 12 (6.7%) developed nonsustained PVT during or shortly after the infusion (11 of 15 occurred during the first infusion). Ibutilide given in repeated doses is highly effective compared to placebo in rapidly terminating chronic atrial fibrillation or flutter and under monitored conditions is a potential alternative to currently available cardioversion options.