Boston, MA - Dronedarone (Sanofi-Aventis)—dubbed the "son of amiodarone"—is better than placebo at maintaining sinus rhythm in patients with atrial fibrillation (AF) and at reducing ventricular rate when arrhythmia recurs, results of the European Trial in Atrial Fibrillation or Flutter Patients Receiving Dronedarone for the Maintenance of Sinus Rhythm (EURIDIS) and American-Australian-African Trial with Dronedarone in Atrial Fibrillation or Flutter Patients for the Maintenance of Sinus Rhythm (ADONIS) show. The trials were first presented three years ago at the European Society of Cardiology meeting in Munich; now Dr Bramah N Singh (University of California, Los Angeles) and colleagues report the full results in the September 6, 2007 issue of the New England Journal of Medicine [1].

As previously reported by heartwire, dronedarone is thought to have the therapeutic potential to replace amiodarone, but because it has no iodine group and is less lipophilic than the parent compound, dronedarone is believed to have fewer side effects and less pulmonary and thyroid toxicity.

EURIDIS included 612 patients, with 411 receiving 400-mg dronedarone twice daily and 201 receiving placebo, and ADONIS included 625 patients, with 417 receiving dronedarone 400 mg twice daily and 208 receiving placebo. At the time of randomization, all patients had been in sinus rhythm for at least one hour and had had at least one ECG-documented episode of AF in the previous three months. Trial drug or placebo was continued for 12 months.

At 12 months, 64% of patients in the combined dronedarone group from both trials had experienced AF reoccurrence, compared with 75% of placebo-treated patients. Time to AF recurrence—the primary end point of the trial—was significantly longer in dronedarone-treated patients.

Ventricular rate at the time of arrhythmia recurrence was also lower in both trials for dronedarone-treated patients than placebo-treated patients. A post hoc analysis indicated that hospitalization or mortality at 12 months was significantly lower in the dronedarone group than in the placebo group.

There were no major differences in adverse events in either group, although elevated serum creatinine levels were more common in the dronedarone group than in the placebo group (2.4% vs 0.2%; p=0.004). Dronedarone-treated patients experienced significantly less hyperthyroidism than placebo-treated patients (8.4% vs 14.1%; p=0.002).

"Dronedarone was significantly more effective than placebo in maintaining sinus rhythm and in reducing the ventricular rate during recurrence of arrhythmia," the authors conclude.

In an accompanying editorial [2], Dr Michael D Ezekowitz (Lankenau Institute for Medical Research and Main Line Hospitals, Wynnewood, PA) writes that the lack of an effect of dronedarone on thyroid is reassuring and in keeping with the anticipated effects of the drug. That said, longer-term, head-to-head trials against amiodarone would be necessary to prove the improved safety profile of the newer agent, particularly in terms of pulmonary fibrosis.

"An important limitation of the two dronedarone trials is the comparison with placebo rather than with active treatment to prevent recurrence of atrial fibrillation," he writes. "The critical comparison should have been between dronedarone and amiodarone, both because amiodarone is highly efficacious in this setting and because the apparent goal in the development of dronedarone was to produce an agent that would be as effective as amiodarone but have fewer side effects. "

Ezekowitz also points out that the potential adverse effects of dronedarone on patients with heart failure—as suggested in the ANDROMEDA trial—remains an "unresolved concern."