Title:Outcomes with Dronedarone in Atrial Fibrillation: What Differences Between Real-World Practice and Trials? A Meta-Analysis and Meta-Regression Analysis
Volume: 23
Issue: 6
Author(s): Igor Diemberger, Giulia Massaro, Maria L.B. Reggiani, Stefano Lorenzetti, Mauro Biffi, Matteo Ziacchi, Cristian Martignani and Giuseppe Boriani
Affiliation:
Keywords:
Atrial fibrillation, dronedarone, meta-analysis, randomized controlled trial, rhythm control, antiarrhythmic drug.
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.