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 physici ans on the management of AF favors the restoration and maintenance of norma l sinus rhythm. This has several potential benefits, including the alleviat ion of arrhythmia-associated symptoms, hemodynamic improvements, and possib ly a reduced risk of thromboembolic events. After normal sinus rhythm has b een restored, antiarrhythmic therapy is necessary to reduce the frequency o f 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 i n the context of patients with structural heart disease. Flecainide and pro pafenone are well tolerated and effective in maintaining sinus rhythm in pa tients 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 of AF and atrial flutter), and azimilide (st ill to be approved) in patients with AF and structural heart disease. To da te, amiodarone and sotalol still hold the greatest interest, and although c ontrolled clinical trials with these agents have been few,a number are in p rogress and some have been recently completed. These agents are effective i n maintaining normal sinus rhythm in patients with paroxysmal and persisten t AF and are associated with a low incidence of proarrhythmia when used app ropriately. Because of the relative paucity of placebo-controlled trials of antiarrhythmic agents in patients with AF, experience until recently has t ended to dictate treatment decisions. Increasingly, selection of drug thera py is being based on a careful and individualized benefit-risk evaluation b y means of controlled clinical trials, an approach that is likely to domina te the overall approach to the control of atrial fibrillation in the larges t numbers of cases of the arrhythmia. Pharmacologic therapy is likely to be dominated by compounds that exert their predominant effect by prolonging a trial repolarization, (C)1999 by Excerpta Medica, Inc.