A Review of Class III Antiarrhythmic Agents for Atrial Fibrillation: Maintenance of Normal Sinus Rhythm

Abstract

A noteworthy shift from class I to class III antiarrhythmic agents for suppression of atrial fibrillation has occurred. Sotalol, amiodarone, and dofetilide have been evaluated for their ability to maintain sinus rhythm in patients with chronic atrial fibrillation. All of these agents are moderately effective; however, amiodarone appears to be most efficacious. Aside from their common class III actions, these agents have profoundly different pharmacologic, pharmacokinetic, safety, and drug interaction profiles that help guide drug selection. Amiodarone and dofetilide are safe in patients who have had a myocardial infarction and those with heart failure. The safety of commercially available d,l-sotalol in these patients is poorly understood. Torsades de pointes is the most serious adverse effect of sotalol and dofetilide, and risk increases with renal dysfunction. Amiodarone has minimal proarrhythmic risk but has numerous noncardiac toxicities that require frequent monitoring. Overall, an ideal antiarrhythmic agent does not exist, and drug selection should be highly individualized.

Risk Prediction for Adverse Events during Initiation of Sotalol and Dofetilide for the Treatment of Atrial Fibrillation

“…Of the 37 DF patients treated with CCBs who experienced these types of AEs, 16 patients were on diltiazem, 11 patients were on amlodipine, and 10 were on verapamil. DF is metabolized in part by the CYP3A4 isoenzyme of the cytochrome P450 system and inhibitors of the CYP3A4 isoenzyme, such as diltiazem and verapamil, can potentially increase dofetilide levels . Independent of this, verapamil also increases gastrointestinal blood flow, leading to increased DF absorption.…”

Intravenous and oral administration of amiodarone for the treatment of recent onset atrial fibrillation after digoxin administration

“…Amiodarone has numerous electrophysiological effects that probably contribute to its anti-arrhythmic efficacy [18]. Although it is considered to be a class III anti-arrhythmic agent, it also possesses high affinity for inactive sodium channels, non-competitive beta-blocker activities and is also a weak calcium channel blocker [19].…”

KB130015, A New Amiodarone Derivative with Multiple Effects on Cardiac Ion Channels

“…Therefore, effective prevention and treatment of arrhythmias constitute major challenges in the therapy of cardiovascular diseases and their complications. Among available pharmacological agents, class III antiarrhythmic drugs [according to the classifications of Singh and Vaughan -Williams (79,88,89)] have emerged as most useful in the prevention and treatment of ventricular and supraventricular arrhythmias (47,83). Their beneficial effects are due to a prolongation of action potential duration and of refractoriness.…”