Azimilide is an investigational Class III antiarrhythmic that has been developed for treating both supraventricular and
ventricular tachyarrhythmias. Similar to other Class III antiarrhythmics,
azimilide prolongs myocardial repolarization in a dose-dependent manner by increasing the action potential duration, QT interval, and effective refractory period. The most frequent reported side effect is
headache, with rare serious adverse events of early reversible
neutropenia and
Torsades de Pointes. In long-term follow up, the patient withdrawal rate has been low.
Azimilide has very predictable pharmacokinetics, is predominantly hepatically metabolized, and has no significant drug interactions with
digoxin or
warfarin. In animal models,
azimilide has been shown to be very effective in suppressing both atrial and
ventricular tachyarrhythmias, decreasing the defibrillation energy requirement, and preventing post-
myocardial infarction ventricular tachycardia and fibrillation. Clinically, in a series of 4 double-blind, randomized, placebo-controlled trials, the
Azimilide Supraventricular
Arrhythmia Program which included over 1000 patients and approximately 70% with structural
heart disease,
azimilide showed a significant prolongation in the time to first recurrence of
paroxysmal supraventricular tachycardia or
atrial fibrillation/flutter. With respect to
ventricular tachyarrhythmias, the
AzimiLide post-
Infarct surVival Evaluation Trial was a large randomized, multinational, prospective, placebo-controlled study in recent survivors of
myocardial infarction at high risk for
sudden cardiac death. After 1 year of follow-up, this study showed no statistical difference in all-cause mortality between placebo and
azimilide. However,
azimilide did statistically reduce the incidence of new
atrial fibrillation. Further trials are necessary to evaluate the efficacy of
azimilide in patients with symptomatic ventricular arrhythmias.