Purpose: The purpose of this study is to assess the safety of long-term use of azimilide in patients with atrial fibrillation/flutter and/or paroxysmal sypraventricular tachycardia. Atrial fibrillation is the most common cause of clinically significant sustained tachycardia and occurs in up to 12% of individuals over age 75. Incidence increases with each decade of life. Furthermore, atrial fibrillation is responsible for up to 1/3 of thromboembolic strokes. Anticoagulation, pharmacologic control of the ventricular response, and antiarrhythmic pharmacotherapy have been the main stays of treatment for atrial fibrillation. However, the selection of available antiarrhythmic drugs, and their efficacy, are limited. Specifically, of available antiarrhythmic agents, only sotalol and amiodarone are considered safe in patients with underlying heart disease. Atrial fibrillation is most often associated with valvular, ischemic, or hypertrophic heart disease, limiting the use of available type I antiarrhythmic agents. Further, the class III agents sotalol and amiodarone are potent negative chronotropic agents which limits their usefulness in patients with atrial fibrillation in association with sinus node disease (brady-tachy syndrome), also a frequent clinical occurence. Accordingly, there is an important need for the development of new antiarrhythmic drugs with the following characteristics: 1) safety in patients with structural heart disease. 2) absence of significant negative chronotropic effects. One such drug is Azimilide, a class III antiarrhythmic agent with very weak bradycardic effects at test dosing levels, and which appears to be safe when used in individuals with structural heart disease. Methods: This is a multi-center double-blind, placebo-controlled, parallel design clinical trial studying a daily oral dose of 125 mg of azimilide dihydrochloride. Results: Results of the double blind trial of azimilide has been reported in preliminary form (n=89) with demonstration of a significant decreases in mean time to AF recurrence in azimilide treated patients (130 days; 100mg/d and 125mg/d) comparted with control (17 days, p (log rank) of 0.002). Significance: The significance of this clinical research program is to test the safety and efficacy of this promising new antiarrhythmic drug in the treatment of atrial fibrillation. Atrial fibrillation is the most common cause of clinically significant sustained tachycardia and occurs in up to 12% of individuals over age 75. Incidence increases with each decade of life. Furthermore, atrial fibrillation is responsible for up to 1/3 of thromboembolic strokes. Future Plans: Phase III trials of Azimilide are ongoing, and it is anticipated that currently enrolled patients will be followed prospectively for a total of 24 months. After completion of the phase III trials of Azimilide for treatment of atrial fibrillation, further studies of the safety and efficacy of this new antiarrhythmic agent to control paroxysmal atrial fibrillation in specific clinical circumstances are envisioned. These studies will be conducted under separate protocol.
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