Will dronedarone help patients with atrial fibrillation to maintain sinus rhythm?

For every 9 patients who take dronedarone for 1 year, 1 fewer will experience a recurrence of atrial fibrillation (AF). What we really need are comparisons of this new drug with older drugs; longer studies; and studies that evaluate patient-oriented outcomes, such as symptom control and quality of life. (LOE = 1b)

Singh BN, Connolly SJ, Crijns HJ, et al, for the EURIDIS and ADONIS Investigators. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N Engl J Med 2007;357(10):987-999.  [PMID:17804843]

Randomized controlled trial (double-blinded)

Industry

Concealed

Outpatient (specialty)

Previous studies (most notably N Engl J Med 2002;347(23):1825-1833) have shown that rate control with anticoagulation is at least as good as rhythm control for patients with chronic AF. Some patients and clinicians continue to attempt rhythm control for quality of life and symptomatic reasons, although current anti-arrhythmics, such as amiodarone, have serious adverse effects. Dronedarone is a cousin to amiodarone, and has been engineered to reduce thyroid and pulmonary adverse effects. It also has a much shorter half-life of 1 or 2 days, compared with 1 to 2 months for amiodarone. This study is actually 2 separate but identical studies, one in Europe and one conducted in North America, Australia, South Africa, and Argentina; I will report only the combined results, since they were similar between studies. This manufacturer-sponsored study enrolled 1237 adults with at least 1 episode of AF in the past 3 months; the authors excluded patients with bradycardia, NYHA class III or IV heart failure, sinus node disease without a pacemaker, at least second-degree atrioventricular block, or who were taking class I or III antiarrhythmics. Analysis was by intention to treat and groups were balanced at the start of the study. Patients were randomized in a 1-to-2 ratio to either dronedarone 400 mg twice daily by mouth or matching placebo. During an initial 7-day screening period, patients who were not in sinus rhythm were cardioverted and included in the study if they remained in sinus rhythm for at least 1 hour. Patients were followed up at regular intervals for 12 months. Patients had a mean age of 63 years, 31% were women, and 97% were white. The mean time to recurrence of AF was longer in the dronedarone group (116 vs 53 days) and fewer dronedarone-treated patients experienced a recurrence at 12 months (64% vs 75%; number needed to treat [NNT] = 9; 95% CI, 6 - 19). The authors also report a lower risk of hospitalization or death with dronedarone at 12 months (22.8% vs 30.9%; NNT = 12; 7- 36). However, since there were only a handful of deaths (approximately1% in each group) most of this difference is due to the need for hospitalization, which is probably related to recurrent AF. The authors do not report on quality of life or symptomatic relief despite their initial contention that this was an important reason for choosing rhythm control. Adverse effects, including pulmonary and thyroid adverse effects, were no worse with active treatment.