Dronedarone: A Promising Alternative for the Management of Atrial Fibrillation

Abstract

Atrial fibrillation (AF) is the most frequently encountered chronic arrhythmia associated with significant morbidity. It is generally encountered in the elderly, and will presumably become more prevalent in the future due to the increasing proportion of the elderly in the population. Major studies on AF have demonstrated no significant difference between rhythm and rate control in terms of mortality. However, young population with new-onset or lone AF, or patients in whom the maintenance of sinus rhythm is a must (due to recurrent thromboembolic events etc.) still gives rise to significant concerns related to the obligatory long-term prophylaxis. The long-term administration of the currently available conventional agents (amiodarone, dofetilide, sotalol, propafenone,flecainide etc.) is considered as a 'double edged sword' due to the presence of life-threatening adverse effects including pro-arrhythmia and organ toxicity associated with these agents. Several molecules are being developed for the management of AF. However, only a few novel agents confer promising results with respect to safety and efficacy issues in the major studies. Dronedarone is an amiodarone analogue without iodine moiety in its structure, and is similar to amiodarone with regard to its structural and electrophysiological properties. Dronedarone is largely denuded of the potentially life-threatening adverse effects of anti-arrhythmics. Major clinical studies have demonstrated both rhythm and rate-controlling efficacy of dronedarone compared to placebo without any serious adverse effects in patients with AF. However, the ANDROMEDA trial, a large scale study including patients hospitalized for symptomatic congestive heart failure (with severely depressed left ventricular systolic functions) was prematurely terminated due to the increased mortality in the dronedarone arm compared to placebo indicating a lack of safety in this group of patients. Conversely, the recently published ATHENA study (including more than 4,600 high risk patients, but excluding those with severe heart failure) demonstrated a significant reduction in cardiovascular hospitalizations and cardiovascular mortality with dronedarone compared to placebo. In contrast, the DIONYSOS study, comparing dronedarone with amiodarone, demonstrated better safety, but lower efficacy of dronedarone for the maintenance of sinus rhythm in patients with AF. Further clinical trials (including head to head comparison with other conventional anti-arrhythmics) are still required to determine the place of dronedarone in the management of AF. The present review focuses on basic and clinical aspects of dronedarone, a novel agent for the management of AF.