Dronedarone ( Multaq ) is a non-iodinated benzofuran derivative with antiarrhythmic properties. In placebo-controlled atrial fibrillation ( AF ) trials, the drug was found to have divergent effects on endpoints such as cardiovascular death or hospitalization.
The objective of this meta-analysis of all placebo-controlled studies was to provide insights on possible reasons for these divergent effects.
Individual data on 9664 patients were used from all atrial fibrillation placebo-controlled studies.
The primary outcome measure was cardiovascular death. Cardiovascular hospitalization and hospitalization for heart failure were secondary endpoints.
Predefined procedures were used to reduce inter-study heterogeneity adjusting for important baseline variables using a Cox model. Despite adjustments, a significant inter-trial heterogeneity of the outcome of cardiovascular mortality persisted ( P-value of 0.005 for the treatment effect × study interaction ).
Further analyses were conducted in subgroups based on baseline clinical criteria: Digoxin co-prescription, advanced heart failure, coronary artery disease, or the presence of permanent atrial fibrillation.
These analyses allowed the calculation of a global treatment effect in two important patient subgroups, those with permanent atrial fibrillation in whom there was harm with respect to cardiovascular mortality [ hazard ratio ( HR ) = 2.32; 95% confidence interval (CI) 1.13-4.75 ] and hospitalization for heart failure ( HR = 1.674; 95% CI 1.05-2.67 ); and those with non-permanent AF in whom there was benefit in terms of cardiovascular hospitalization [ HR = 0.751 95% CI ( 0.68-0.83 ) ].
In conclusion, this meta-analysis has demonstrated significant heterogeneity of Dronedarone treatment effects across the placebo-controlled randomized trials.
The most important predictor of a harmful effect of Dronedarone on cardiovascular death and heart failure hospitalization was the presence of permanent atrial fibrillation. ( Xagena )
Hohnloser SH et al, Europace 2014;16:1117-1124