Azimilide, a novel class III antiarrhythmic agent, blocks both the slowly activating (IKs) and rapidly activating (IKr) components of the delayed rectifier
potassium current, which distinguishes it from conventional
potassium channel blockers such as
sotalol and
dofetilide, which block only IKr.
Azimilide is being developed to prolong the time to recurrence of
atrial fibrillation,
atrial flutter, and
paroxysmal supraventricular tachycardia in patients with and without structural
heart disease.
Azimilide is also being studied for its role in prevention of
sudden cardiac death in high-risk patients after
myocardial infarction (MI). Preclinical and clinical studies indicate that
azimilide prolongs cardiac refractory period in a dose-dependent manner, as manifested by increases in action potential duration, QTc interval, and effective refractory period.
Azimilide does not affect PR or QRS interval and minimally affects hemodynamic properties such as blood pressure and heart rate. Its in vivo effects appear to be rate-independent and are maintained under ischemic or hypoxic conditions, properties of potential clinical significance.
Azimilide has shown excellent efficacy (>85%) in suppressing supraventricular arrhythmias in a variety of dog models. It also suppressed complex ventricular arrhythmias in infarcted dogs and, in a
sudden death cardiac model, decreased mortality.
Azimilide pharmacokinetics are very predictable. The
drug is completely absorbed, and the extent of absorption is not affected by food. It can be administered once daily. Clinical data suggest that dose adjustments of
azimilide are not required for age, gender, hepatic or renal function, or concomitant use of
digoxin or
warfarin.
Azimilide has a good safety profile in open-label safety studies in >800 supraventricular
arrhythmia patients, most with structural
heart disease. The incidence of serious adverse events, including
torsade de pointes, is low. The rate of patient withdrawal from long-term studies is also encouragingly low. Unlike
amiodarone,
azimilide has shown no evidence of pulmonary or
ocular toxicity.
Azimilide is expected to provide a unique new
therapy for the prevention of supraventricular arrhythmias and
sudden cardiac death when Phase III clinical trials are complete and safety and efficacy are confirmed.