Multaq (dronedarone), in addition to standard therapy, significantly reduced the risk of first cardiovascular (CV) hospitalization or death by 24 percent in patients with atrial fibrillation or a recent history of these conditions, according to the ATHENA trial published today in the New England Journal of Medicine.
"The ATHENA trial is the first trial to show a reduction in the incidence of cardiovascular hospitalization or death in patients taking an anti-arrhythmic drug for atrial fibrillation," commented the study's principal investigator Stefan H. Hohnloser, MD, from the Goethe University's division of clinical electrophysiology in Frankfurt, Germany.
Hohnloser and colleagues conducted a multicenter trial to evaluate the use of dronedarone in 4,628 patients with atrial fibrillation, who had additional risk factors for death. Patients were randomly assigned to receive dronedarone, 400 mg twice a day, or placebo. The primary outcome was the first hospitalization due to CV events or death and the secondary outcomes were death from any cause, death from CV causes, and hospitalization due to CV events.
The mean follow-up period was 21 months, with the study drug discontinued prematurely in 30.2 percent receiving dronedarone and in 30.8 percent receiving placebo, "mostly because of adverse events," according to the authors.
They reported that the primary outcome occurred in 31.9 percent in the dronedarone group and in 39.4 percent in the placebo group, with a hazard ratio for dronedarone of 0.76.
According to the authors, there were 116 deaths (5 percent) in the dronedarone group and 139 (6 percent) in the placebo group. There were 63 deaths from cardiovascular causes (2.7 percent) in the dronedarone group and 90 (3.9 percent) in the placebo group, "largely due to a reduction in the rate of death from arrhythmia with dronedarone."
The researchers reported that the dronedarone group had higher rates of bradycardia, QT-interval prolongation, nausea, diarrhea, rash and an increased serum creatinine level than the placebo group. Rates of thyroid- and pulmonary-related adverse events were not significantly different between the two groups.
Stuart J. Connolly, MD, director of the division of cardiology at McMaster University in Ontario, Canada, and co-principal investigator of the ATHENA trial said that the "clinical benefits observed with dronedarone in ATHENA occurred without a significantly higher rate of thyroid or pulmonary disorders compared with placebo reported within the study period."
The investigators also noted that the time to first recurrence of atrial fibrillation was increased from a median of 53 days in the control group to 116 days in the dronedarone group. Also, the drug decreased the mean ventricular rate during the recurrence of atrial fibrillation, from 117 to 103 beats per minute.
The Paris-based Sanofi-Aventis, maker of Multaq, financed the study.