Drug choices in the treatment of atrial fibrillation

When considering therapy for atrial fibrillation (AF), the dominant issues are rate control, anticoagulation, rhythm control, and treatment of any underlying disorder. Drug choices for rate control include beta-blockers, verapamil and diltiazem, and digitalis as first-line agents, with consideration of other sympatholytics, amiodarone, or nonpharmacologic approaches in resistant cases. Anticoagulation may be accomplished with aspirin or warfarin, with the latter preferred in all older or high-risk patients. Antiarrhythmic drug therapy may be used (1) to produce cardioversion (most effective with ibutilide or class IC agents in recent onset AF); (2) to facilitate electrical conversion (class III agents); (3) to prevent early reversion after cardioversion; (4) to maintain sinus rhythm during chronic therapy; and/or (5) to facilitate conversion of fibrillation to flutter, which may then be amenable to termination or prevention with antitachypacing or ablative techniques. Antiarrhythmic drug selection for AF is guided by efficacy considerations (most drugs are similar), by convenience, cost, and discontinuation considerations; and, most importantly, by safety considerations. When possible, agents with serious organ toxicity potential and proarrhythmic risk should be avoided as first-line choices. In structurally normal hearts, class IC antiarrhythmic drugs are least proarrhythmic and least organ toxic (when considered together). In normal hearts, sotalol, dofetilide, and potentially azimilide also appear to have attractive profiles. Amiodarone has low proarrhythmic risk but can produce bradyarrhythmias and toxicity. In hypertrophied hearts, the risk of torsade de pointes with class III/IA agents is enhanced, whereas in ischemia or conditions with impaired cell contact, whether functionally (as by ischemia) or anatomically (as by fibrosis, infiltration, etc), proarrhythmic risk with class I antiarrhythmic drugs (sustained ventricular fibrillation/flutter) is greatly increased. The class I drugs should be avoided in these circumstances. Additional issues to consider are where to initiate therapy (in- or outpatient), what follow-up protocols to use, and whether to limit therapy to proprietary drugs or to allow generic formulation substitution. Each of these considerations is detailed in this article.