Abstract
Dronedarone is a new multichannel blocker, structurally related to amiodarone but free of iodine and less lipophilic and so expected to be free of iodine-related organ toxicity and tissue accumulation. The drug was developed for the treatment of atrial fibrillation (AF). The phase II Dronedarone Atrial FibrillatioN study after Electrical cardioversion (DAFNE) study established 400 mg twice-daily dosing (bid) as the standard dose for dronedarone in the maintenance of sinus rhythm. In the pivotal phase III European Trial In Atrial Fibrillation Or Flutter Patients Receiving Dronedarone For The Maintenance of Sinus Rhythm/ American-Australian-African Trial With Dronedarone In Atrial Fibrillation/flutter Patients For The Maintenance of Sinus Rhythm (EURIDIS/ADONIS) studies in patients with paroxysmal/persistent AF and atrial flutter, dronedarone significantly prolonged the mean time to first AF/flutter recurrence. Although dronedarone proved to be safe in these AF studies, a trial in patients with severe congestive heart failure was prematurely stopped because of excess mortality in the dronedarone relative to the control group. This finding prompted the conduct of a large randomized study in more than 4600 patients with nonpermanent AF, which used the primary end point of time to first cardiovascular (CV) hospitalization or death. Dronedarone significantly reduced the incidence of the primary as well as several secondary end points among which CV mortality was the most significant one. The results of this development program led to the approval of dronedarone for use in patients with AF in several jurisdictions. This article provides a short summary of the most important findings during the clinical development of dronedarone.