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What niche will newer class III antiarrhythmic drugs occupy?
1Division of Cardiology 111E, VA Medical Center of West Los Angeles, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA. bsingh@ucla.edu
Abstract:
The decline in the use of sodium channel blockers has led to an expanding use of b-blockers and complex class III agents such as sotalol and amiodarone for controlling cardiac arrhythmias. Success with these agents in the context of their side effects has spurred the development of compounds with simpler ion channel-blocking properties with less complex adverse reactions. The resulting so-called pure class III agents were found to have antifibrillatory effects in atrial fibrillation (AF) and flutter, as well as in ventricular tachyarrhythmias. Pure class III compounds are effective in inducing acute chemical conversion of AF, in preventing paroxysmal AF, and in maintaining sinus rhythm in patients with persistent AF restored to sinus rhythm. Examples of such compounds are dofetilide, which selectively blocks IKr, and ibutilide, available only as an intravenous agent, which blocks the IKr and augments the inactivated Na+ current in atrial myocytes. Dofetilide and ibutilide have been introduced into clinical practice. Azimilide is the first of the class III agents that blocks both components (IKr and IKs) of the delayed rectifier current, which may confer certain electrophysiologic advantages. The potential therapeutic niche of ibutilide, dofetilide, and azimilide in the control of cardiac arrhythmias forms the basis of this review.
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