The rate vs rhythm debate

The rate vs rhythm debate

Rate control vs rhythm control for atrial fibrillation continues to be debated with most of the evidence falling on the side of rate control in recent years, primarily because of adverse effects from anti-arrhythmics. A new drug may change that however. Dronedarone, a derivative of amiodarone, lowers the hospitalization rate and death rate in atrial fibrillation according to a new phase 3 study. More than 4600 patients with atrial fibrillation and one additional risk factor for death (diabetes, stroke, CHF) were randomized to dronedarone 4 mg twice a day or placebo. The primary outcome was first hospitalization due to cardiovascular event or death. After follow-up of 21 months, 30% of patients in the treatment group and 31% patients in the placebo group stopped the drug prematurely due to adverse events. The primary outcome occurred in 31.9% of patients in the dronedarone group vs 39.4% in the placebo group (hazard ratio, 0.76; 95% confidence interval, 0.69-0.84; P < 0.001). Five percent (5%) of people died in the treatment group vs 6% in the placebo group (P = 0.18). Deaths from cardiovascular causes were 2.7% in the dronedarone group vs 3.9% in the placebo group (P = 0.03). The treatment group had higher rates of bradycardia, QT interval prolongation, nausea, diarrhea, rash, and increased creatinine levels. Dronedarone was not associated with higher rates of thyroid or pulmonary-related adverse events. The authors conclude that dronedarone reduced the risk of hospitalization due to cardiovascular events or death in patients with atrial fibrillation (N Engl J Med 2009;360:668-678). Dronedarone is not yet approved in this country, and is being evaluated for other cardiac arrhythmias as well as atrial fibrillation. A trial in heart failure (ANDROMEDA) was terminated early because of increased mortality associated with dronedarone (N Engl J Med 2008;358:2678-2687).