title: Dronedarone in high-risk permanent atrial fibrillation.
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.).
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON L8L 2X2, Canada. connostu@phri.ca
authors.forename: Stuart J
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authors.lastname: Connolly
authors.forename: A John
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authors.forename: Kui-Hian
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authors.lastname: Stiles
authors.forename: Supachai
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authors.lastname: Tanomsup
authors.forename: Lauri
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authors.lastname: Toivonen
authors.forename: János
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authors.lastname: Tomcsányi
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authors.lastname: Torp-Pedersen
authors.forename: Hung-Fat
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authors.lastname: Vardas
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authors.lastname: Vinereanu
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authors.lastname: Xavier
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authors.forename: Jun-Ren
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authors.forename: Lydie
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authors.lastname: Baret-Cormel
authors.forename: Estelle
authors.initials: E
authors.lastname: Weinling
authors.forename: Christoph
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authors.lastname: Staiger
authors.forename: Salim
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authors.lastname: Yusuf
authors.forename: Susan
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authors.lastname: Chrolavicius
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mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000638:Amiodarone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000097:blood / Q000188:drug therapy*; D001282:Atrial Flutter / Q000188:drug therapy; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000401:mortality; D002908:Chronic Disease; D004077:Digoxin / Q000097:blood / Q000627:therapeutic use; D004311:Double-Blind Method; D000077764:Dronedarone; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000139:chemically induced / Q000453:epidemiology; D006339:Heart Rate / Q000187:drug effects; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D012307:Risk Factors; D020521:Stroke / Q000139:chemically induced / Q000453:epidemiology
chemical_list: D000889:Anti-Arrhythmia Agents; D004077:Digoxin; D000077764:Dronedarone; D000638:Amiodarone