The Odyssey of the synthetic noniodinated amiodarone congener, dronedarone: a grey chapter of the antiarrhythmic drug development
Szegedi Tudományegyetem, Szent-Györgyi Albert Klinikai Központ, Általános Orvostudományi Kar, I. Belgyógyászati Klinika, Szeged
Dronedarone is a novel synthetic noniodinated benzofuran derivative that has been developed to eliminate the adverse effects of the most effective and commonly used antiarrhythmic drug, amiodarone. Dronedarone’s electrophysiological spectrum is largely similar of the “multichannel” inhibitor/multitarget amiodarone. Some prospective, randomized, controlled clinical trials (DAFNE, EURIDIS/ADONIS, ERATO, ATHENA) have suggested safety, sinus rhythm maintaining and/or ventricular rate controlling efficacy of dronedarone (800 mg/day). In contrary, ANDROMEDA and PALLAS trials raised safety concerns for patients with systolic/congestive heart failure (CHF) and severe left ventricular dysfunction (LVEF ≤35%; NYHA III-IV) by doubling cardiovascular mortality. Dronedarone could be a useful second- or third-line agent for some of the low-risk symptomatic intermittent (paroxysmal/persistent) AF patients requiring rhythm control. Despite the fact that dronedarone does not contain iodine, severe liver injury (requiring urgent liver transplantation) and lung toxicity were reported. Dronedarone should not be used for patients with CHF, those with left ventricular dysfunction (LVEF ≤35%) and/or permanent AF. Until now, dronedarone’s place in the management of AF remains largely undefined and grey, primarily because of its relative lack of efficacy and safety. ‘The scenario related to dronedarone is an example of enthusiasm exceeding the evidence and one has to struggle to find a low-risk atrial fibrillation population/patient where it would more effective and not be unsafe”, said Kaul, a FDA panel member.