Dronedarone significantly reduces the incidence of cardiovascular hospitalization or death in moderate-risk and high-risk patients with paroxysmal or persistent atrial fibrillation or flutter, according to a presentation at the Heart Rhythm Society's Heart Rhythm 2008 meeting.

The ATHENA Trial was a placebo-controlled, double-blind, morbidity and mortality study designed to assess the efficacy of dronedarone for prevention of cardiovascular hospitalization or death from any cause in patients with atrial fibrillation or atrial flutter that randomized 4,628 patients with arrhythmia or history of the disorder to dronedarone 400 mg twice daily or placebo, with a minimum follow-up of one year.

Primary study outcome was time to first cardiovascular hospitalization or death from any cause and secondary outcomes were total mortality, cardiovascular mortality, and cardiovascular hospitalization. ATHENA was performed at 551 centers in 37 countries.

Dronedarone is a non-iodinated analog of amiodarone with multi-channel blocking effects and anti-adrenergic properties that was developed for treatment of atrial fibrillation and atrial flutter.

The patients enrolled in ATHENA represent the typical elderly population (mean age, 72 years) who are at risk for hospitalization. Structural heart disease was present in 60 percent of patients and 82 percent of patients who were also receiving therapy for hypertension. Roughly 25 percent of patients were in atrial fibrillation or atrial flutter at time of randomization. Coronary artery disease was present in 30 percent of patients, and 20 percent of patients had NYHA Class II or III symptoms at enrollment. Both patients with paroxysmal and persistent atrial fibrillation were included.

Dronedarone resulted in a significant reduction in the primary endpoint of time to first cardiovascular hospitalization or all cause mortality. There were fewer deaths in the dronedarone arm than placebo, although the difference was not significant. The primary endpoint was mainly driven by a reduction in time to first cardiovascular hospitalization, due to a significant reduction in hospitalization for atrial fibrillation. There were also fewer hospitalizations for acute coronary syndrome in the dronedarone arm compared with placebo. The pre-specified secondary endpoint, cardiovascular death, was significantly lower in the dronedarone group compared to placebo.

Principle investigator Stefan H. Hohnloser, MD, of J.W. Goethe University in Frankfurt, Germany, said that the ATHENA trial was not designed to study the effect of dronedarone on the maintenance of sinus rhythm. Similar trials have already been performed with dronedarone (EURIDIS and ADONIS trials). Hohnloser stated that the ATHENA trial actually represents a change in the paradigm for treatment of atrial fibrillation, in which the goal of therapy is not focused on rate control or rhythm control, but instead on reducing hospitalizations and mortality. In fact, the ATHENA investigators did not actively follow the rates of atrial fibrillation or recurrence in the dronedarone or placebo groups.