Dronedarone: a new antiarrhythmic agent for the treatment of atrial fibrillation

In the armamentarium for rhythm control, amiodarone has been a mainstay of therapy for the management of atrial fibrillation (AF). Although amiodarone has shown to be effective in maintaining sinus rhythm, it has many extracardiac adverse effects. Dronedarone, a benzofuran amiodarone derivative, is structurally modified to reduce toxicities often associated with chronic amiodarone therapy. With the addition of a methylsulfonyl group, dronedarone is less lipophilic, has lower tissue accumulation, and a much shorter serum half-life of 24 hours compared with amiodarone. Dronedarone is also designed without the iodine moieties that are responsible for thyroid dysfunctions associated with amiodarone. Similar to amiodarone, dronedarone exhibits electrophysiologic characteristics of all 4 Vaughan Williams classifications. Phase III clinical trials have shown dronedarone to be effective at reducing ventricular rate, reducing recurrence of AF, and reducing cardiovascular morbidity and mortality in patients with AF or atrial flutter (AFL). However, dronedarone was associated with increased mortality in one study that included patients with severe heart failure (HL) and left ventricular dysfunction. Overall, dronedarone appears to be well tolerated. The most common side effects are gastrointestinal in nature and include nausea, vomiting, and diarrhea. Because of its more favorable adverse effect profile, dronedarone is likely to be a useful addition to the therapeutic management of AF. However, further comparative studies with amiodarone are needed to define dronedarone's place in therapy more clearly.