Dronedarone in high-risk permanent atrial fibrillation.
Publication/Presentation Date
12-15-2011
Abstract
BACKGROUND: Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation.
METHODS: We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalization for a cardiovascular cause or death.
RESULTS: After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P=0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P=0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P=0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P=0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P=0.02).
CONCLUSIONS: Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients. (Funded by Sanofi-Aventis; PALLAS ClinicalTrials.gov number, NCT01151137.).
Volume
365
Issue
24
First Page
2268
Last Page
2276
ISSN
1533-4406
Published In/Presented At
Connolly, S. J., Camm, A. J., Halperin, J. L., Joyner, C., Alings, M., Amerena, J., Atar, D., Avezum, Á., Blomström, P., Borggrefe, M., Budaj, A., Chen, S. A., Ching, C. K., Commerford, P., Dans, A., Davy, J. M., Delacrétaz, E., Di Pasquale, G., Diaz, R., Dorian, P., … PALLAS Investigators (2011). Dronedarone in high-risk permanent atrial fibrillation. The New England journal of medicine, 365(24), 2268–2276. https://doi.org/10.1056/NEJMoa1109867
Disciplines
Medicine and Health Sciences
PubMedID
22082198
Department(s)
Department of Medicine, Cardiology Division
Document Type
Article