Efficacy of intravenous ibutilide for rapid termination of atrial fibrillation and atrial flutter: dose-response study

Objectives. Currently available antiarrhythmic drugs have limited efficacy for short-term, rapid termination of atrial fibrillation and atrial flutter. Background. Ibutilide fumarate is an investigational class III antiarrhythmic agent that prolongs repolarization by increasing the slow inward sodium current and by blocking the delayed rectifier current. It can be administered intravenously and has rapid onset of electrophysiologic effects. Methods. The efficacy and safety of ibutilide were studied in 200 patients with atrial flutter >3 b in duration or atrial fibrillation 3 h to 90 days in duration. Patients were randomized to receive single intravenous dose of placebo or an infusion of ibutilide fumarate at 0.005, 0.010, 0.015, or 0.025 mg/kg body weight over 10 min. Conversion was defined as termination of the atrial arrhythmi during or within 60 min after infusion. Forty-one patients received placebo and 159 received ibutilide (0.005 mg/kg [n = 41], 0.010 mg/kg [n = 40], 0.015 mg/kg [n = 38] or 0.025 mg/kg [n = 40]). Results. The arrhythmi terminated in 34% of drug-treated patients. The rates of successful arrhythmi termination were 3% for placebo and 12%, 33%, 45% and 46%, respectively, for 0.005-, 0.010-, 0.015- and 0.025-mg/kg ibutilide. The placebo and 0.005-mg/kg ibutilide groups had lower success rates than all other dose groups (p < 0.05). The mean time to termination of the arrhythmi was 19 min (range 3 to 70) from the start of infusion. Successful arrhythmi termination was not affected by enlarged left atrial diameter, decreased ejection fractions, presence of valvular heart disease or the use of concomitan medications (beta-adrenergic blocking agents, calcium channel blocking agents or digoxin). Arrhythmi termination was not predicted by the magnitude of corrected QT interval prolongation but was associated with shorter duration of atrial arrhythmia. The most frequent adverse events in ibutilide-treated patients were sustained and nonsustained polymorphic ventricular tachycardi (3.6%). All patients with sustained polymorphic ventricular tachycardi were successfully treated with direct current cardioversion and had no recurrence. The occurrence of proarrhythmi did not correlate with ibutilide plasm concentration. Conclusions. These dat demonstrate that ibutilide is able to rapidly terminate atrial fibrillation and atrial flutter.