title: Outcomes with Dronedarone in Atrial Fibrillation: What Differences Between Real-World Practice and Trials? A Meta-Analysis and Meta-Regression Analysis.
abstract: Dronedarone was found to have divergent safety profiles in randomized controlled trials (RCT) in term of cardiac death and overall mortality. We decided to evaluate all available evidence on the cardiovascular safety of this drug. A systematic search was made of the MEDLINE and the Cochrane Central Register of Controlled Trials from January 2003 through April 2016 for RCT comparing dronedarone to placebo/active control, to provide the most accurate estimate of the effects of this agent and observational cohort studies (OBS) reporting clinical outcomes in patients treated with dronedarone, according to current guidelines, to obtain a real-life comparator for the findings summarized by RTC analysis. The literature search yielded 2335 papers and after careful review we identified 12 RCT and 7 OBS studies. RCT meta-analysis showed that, despite high heterogeneity, dronedarone was not associated with increased all-cause mortality [OR (Odds Ratio) 1.36, 95%CI (Confidence Interval) 0.79-2.33; p=0.732, I2=57.0%] or cardiovascular mortality [OR 1.51 95%CI 0.74-3.08; p=0.860, I2=64.4%]. OBS studies had a trend toward a better survival with respect to RCT [ES (Effect Size) 2.03, 95%CI 0.53-3.53 vs. ES 3.03, 95%CI 1.23-4.83; p=0.115], reaching the significance when restricted to the cardiovascular mortality [ES 0.52, 95%CI 0.36-0.69 vs. ES 1.86, 95%CI 0.62-3.09; p<0.001]. Two variables, co-adiministration of digoxin and prevalence of non-permanent AF completely abolished the dishomogeneity among the analyzed RCT studies. In conclusion, use of dronedarone for prophylaxis of AF recurrences is not associated with an increased risk of death, either cardiovascular or total, and combination with digoxin should be avoided.
authors.affiliation: Cardiology Unit; Department of Experimental, Diagnostic and Specialty Medicine; University of Bologna; Policlinico S. Orsola- Malpighi, Bologna. Italy.
authors.forename: Igor
authors.initials: I
authors.lastname: Diemberger
authors.affiliation: Cardiology Unit; Department of Experimental, Diagnostic and Specialty Medicine; University of Bologna; Policlinico S. Orsola- Malpighi, Bologna. Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Massaro
authors.affiliation: Cardiology Unit; Department of Experimental, Diagnostic and Specialty Medicine; University of Bologna; Policlinico S. Orsola- Malpighi, Bologna. Italy.
authors.forename: Maria L B
authors.initials: MLB
authors.lastname: Reggiani
authors.affiliation: Cardiology Unit; Department of Experimental, Diagnostic and Specialty Medicine; University of Bologna; Policlinico S. Orsola- Malpighi, Bologna. Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Lorenzetti
authors.affiliation: Cardiology Unit; Department of Experimental, Diagnostic and Specialty Medicine; University of Bologna; Policlinico S. Orsola- Malpighi, Bologna. Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Biffi
authors.affiliation: Cardiology Unit; Department of Experimental, Diagnostic and Specialty Medicine; University of Bologna; Policlinico S. Orsola- Malpighi, Bologna. Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Ziacchi
authors.affiliation: Cardiology Unit; Department of Experimental, Diagnostic and Specialty Medicine; University of Bologna; Policlinico S. Orsola- Malpighi, Bologna. Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Martignani
authors.affiliation: Cardiology Division, Department of Diagnostics, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Policlinico di Modena, Via del Pozzo 71, 41124 Modena. Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Boriani
mesh_terms: D000638:Amiodarone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D000077764:Dronedarone; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis
chemical_list: D000889:Anti-Arrhythmia Agents; D000077764:Dronedarone; D000638:Amiodarone
keywords: Atrial fibrillation; antiarrhythmic drug; dronedarone; meta-analysis; randomized controlled trial; rhythm control