• Stuart J Connolly, A John Camm, Jonathan L Halperin, Campbell Joyner, Marco Alings, John Amerena, Dan Atar, Álvaro Avezum, Per Blomström, Martin Borggrefe, Andrzej Budaj, Shih-Ann Chen, Chi Keong Ching, Patrick Commerford, Antonio Dans, Jean-Marc Davy, Etienne Delacrétaz, Giuseppe Di Pasquale, Rafael Diaz, Paul Dorian, Greg Flaker, Sergey Golitsyn, Antonio Gonzalez-Hermosillo, Christopher B Granger, Hein Heidbüchel, Josef Kautzner, June Soo Kim, Fernando Lanas, Basil S Lewis, Jose L Merino, Carlos Morillo, Jan Murin, Calambur Narasimhan, Ernesto Paolasso, Alexander Parkhomenko, Nicholas S Peters, Kui-Hian Sim, Martin K Stiles, Supachai Tanomsup, Lauri Toivonen, János Tomcsányi, Christian Torp-Pedersen, Hung-Fat Tse, Panos Vardas, Dragos Vinereanu, Denis Xavier, Jun Zhu, Jun-Ren Zhu, Lydie Baret-Cormel, Estelle Weinling, Christoph Staiger, Salim Yusuf, Susan Chrolavicius, Rizwan Afzal, Stefan H Hohnloser, and PALLAS Investigators.
• Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON L8L 2X2, Canada. connostu@phri.ca
• N. Engl. J. Med. 2011 Dec 15; 365 (24): 226822762268-76.

BackgroundDronedarone 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.MethodsWe 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.ResultsAfter 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).ConclusionsDronedarone 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.).

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