Dronedarone: an emerging agent with rhythm- and rate-controlling effects

Of current antiarrhythmic agents, amiodarone is among the most effective with the additional advantage of having little proarrhythmic potential. However, it can cause potentially serious extracardiac side effects, stimulating the search for safer derivatives. Dronedarone, a new antiarrhythmic drug that is structurally related to amiodarone, lacks an iodine moiety and, thus, amiodarone's iodine-related organ toxicity, while its methane sulfonyl group decreases lipophilicity so shortening half-life and decreasing tissue accumulation. Electrophysiological studies show that dronedarone shares amiodarone's multichannel blocking effects, inhibiting transmembrane Na(+), K(+), Ca(2+), and slow L-type calcium channels, as well as its antiadrenergic effects. Unlike amiodarone, it has little effect at thyroid receptors. Possessing both rate- and rhythm-control properties, dronedarone has proved safe and effective in preventing recurrence of atrial fibrillation (AF) in patients with persistent AF in the Dronedarone Atrial Fibrillation Study After Electrical Cardioversion (DAFNE) trial, the first prospective randomized trial to evaluate its efficacy and safety. Dronedarone has since undergone further extensive evaluation in three pivotal phase III trials. In two sister studies, the European Trial in Atrial Fibrillation or Flutter Patients Receiving Dronedarone for the Maintenance of Sinus Rhythm (EURIDIS) and American-Australian-African Trial with Dronedarone in Atrial Fibrillation/Flutter Patients for the Maintenance of Sinus Rhythm (ADONIS), dronedarone 400 mg b.i.d. showed significant efficacy against placebo in prevention of AF recurrence. Additionally, in patients with permanent AF, dronedarone was highly effective at controlling ventricular rate on top of standard rate-controlling therapies in the Efficacy and Safety of Dronedarone for the Control of Ventricular Rate during Atrial Fibrillation (ERATO) study.