Antiarrhythmic agents for atrial fibrillation: focus on prolonging atrial repolarization

Atrial fibrillation (AF) has been the subject of considerable attention and intensive clinical research in recent years. Current opinion among physicians on the management of AF favors the restoration and maintenance of normal sinus rhythm. This has several potential benefits, including the alleviation of arrhythmia-associated symptoms, hemodynamic improvements, and possibly a reduced risk of thromboembolic events. After normal sinus rhythm has been restored, antiarrhythmic therapy is necessary to reduce the frequency of AF recurrence. In the selection of an antiarrhythmic agent, both efficacy and safety should be taken into consideration. Many antiarrhythmic agents have the capacity to provoke proarrhythmia, which may result in an increase in mortality. This is of particular concern with sodium-channel blockers in the context of patients with structural heart disease. Flecainide and propafenone are well tolerated and effective in maintaining sinus rhythm in patients without significant cardiac disease but with AF. Recent interest has focused on the use of class III antiarrhythmic agents, such as amiodarone, sotalol, dofetilide (recently approved), ibutilide (approved for chemical conversion of AF and atrial flutter), and azimilide (still to be approved) in patients with AF and structural heart disease. To date, amiodarone and sotalol still hold the greatest interest, and although controlled clinical trials with these agents have been few, a number are in progress and some have been recently completed. These agents are effective in maintaining normal sinus rhythm in patients with paroxysmal and persistent AF and are associated with a low incidence of proarrhythmia when used appropriately. Because of the relative paucity of placebo-controlled trials of antiarrhythmic agents in patients with AF, experience until recently has tended to dictate treatment decisions. Increasingly, selection of drug therapy is being based on a careful and individualized benefit-risk evaluation by means of controlled clinical trials, an approach that is likely to dominate the overall approach to the control of atrial fibrillation in the largest numbers of cases of the arrhythmia. Pharmacologic therapy is likely to be dominated by compounds that exert their predominant effect by prolonging atrial repolarization.