Hohnloser, S. H. et al. Effect of dronedarone on cardiovascular events in atrial fibrillation. N. Engl. J. Med. 360, 668–678 (2009).

The antiarrhythmic agent, dronedarone, has been reported to reduce the incidence of cardiovascular death and hospitalization for cardiovascular causes in patients with atrial fibrillation (AF). The ATHENA trial is the first large-scale, randomized, placebo-controlled study in which the effect of an antiarrhythmic drug on cardiovascular outcomes in patients with AF has been assessed.

Rhythm-control therapy is a common approach to the management of AF, but the use of currently available antiarrhythmic medications, such as amiodarone, is limited by their adverse effects. Dronedarone was developed with the aim of reducing the potentially harmful thyroid and pulmonary sequaelae associated with amiodarone.

The ATHENA investigators randomly assigned 4,628 patients with AF or atrial flutter to receive dronedarone 400 mg twice per day or placebo. A history of mild-to-moderate heart failure was prevalent among the study population, but patients with severe heart failure were specifically excluded. During follow-up (mean 21 ± 5 months), significantly fewer patients in the dronedarone group experienced the combined primary outcome event (death from any cause or hospitalization for cardiovascular events) than did those in the placebo group. Although there was no significant difference between the two treatment groups for all-cause mortality, the incidence of cardiovascular death and death from cardiac arrhythmia was significantly lower among patients who received dronedarone compared with the placebo group. Similarly, fewer patients on dronedarone experienced hospitalization for cardiovascular causes than did those assigned to placebo. Although discontinuation of the study drug was high in both treatment groups, more patients in the dronedarone arm than in the placebo arm stopped taking the medication because of an adverse event.

These data from the ATHENA trial indicate that dronedarone could be a safer alternative to amiodarone for patients with AF who have mild-to-moderate heart failure. “A new standard has been set for the future of antiarrhythmic drug development,” says Professor Peter Kowey, of Jefferson Medical College and the Main Line Health System, PA, USA. “Dronedarone deserves approval and marketing as an alternative agent for patients with AF.”