ORLANDO — The novel multichannel-blocking antiarrhythmic agent dronedarone cut the risk of cardiovascular hospitalization or all-cause mortality by 24% in a meta-analysis of five placebo-controlled, randomized trials involving 6,157 patients with atrial fibrillation or atrial flutter.
Although this decrease in the combined end point was driven mainly by fewer cardiovascular hospitalizations, patients on dronedarone (Multaq) also experienced highly significant 29% and 51% reductions in cardiovascular death and sudden death, respectively, Dr. Stefan H. Hohnloser reported at the annual meeting of the American College of Cardiology.
Patients assigned to dronedarone took 400 mg twice daily for a collective 3,684 patient-years.
Dronedarone exhibited a favorable safety profile, most importantly with regard to its reassuringly low proarrhythmia potential. Only one case of torsade de pointes occurred in a dronedarone-treated patient, who had multiple torsade risk factors.
Cardiovascular hospitalization or death from any cause occurred in 25.9% of the dronedarone group compared with 34.3% of those on placebo. This is the only antiarrhythmic agent ever shown to reduce morbidity and mortality in patients with atrial fibrillation or flutter, said Dr. Hohnloser, professor of medicine at J.W. Goethe University, Frankfurt, Germany.
The most common side effects in dronedarone-treated patients were diarrhea or nausea/vomiting, which occurred in 15% of these patients, compared with 9% on placebo. Among those on the antiarrhythmic agent, 10% developed a rash, as did 7% of those on placebo. A rise in serum creatinine level occurred in 4% of those on the drug and 1.1% on of those placebo.
Prior analyses have established that dronedarone is effective both in controlling ventricular rate and in maintaining normal sinus rhythm.
The new meta-analysis incorporated the DAFNE, ADONIS, ATHENA, ERATO, and EURIDIS trials. The meta-analysis is timely, as a Food and Drug Administration advisory panel voted 10–3 in March to recommend marketing approval for dronedarone, a Sanofi-Aventis drug.
Dr. Hohnloser disclosed serving as a paid consultant to Sanofi-Aventis, Cardiome, ARYx Therapeutics, and Bristol-Myers Squibb.