Proarrhythmic Potential of Dronedarone: Emerging Evidence from Spontaneous Adverse Event Reporting

Study Objective To characterize the frequency and type of cardiac events, including torsade de pointes, associated with dronedarone and its structural analog, amiodarone, outside of the clinical trial setting. Design Retrospective analysis. Data Source Spontaneous reports in the United States F ood and D rug A dministration ( FDA ) A dverse E vent R eporting S ystem ( AERS ) database generated between J uly 1, 2009, and J une 30, 2011. Measurements and Main Results All reports of adverse events during the study period were reviewed to identify cardiac events associated with any approved drug in the United States. The type and number of cardiac events associated with dronedarone and amiodarone were determined. Active ingredients were identified using the D rugs@ FDA database, and the M edical D ictionary for R egulatory A ctivities ( MedDRA ) was used to aggregate related adverse events. To avoid redundant reporting, all statistics were generated in reference to unique case identifiers. Dronedarone was associated with more adverse cardiovascular event reports than amiodarone (810 vs 493 reports) during the study period. Dronedarone was also associated with the most reports of torsade de pointes of any approved drug in the U nited S tates (37 reports), followed by amiodarone (29 reports). Reports of ventricular arrhythmias and cardiac arrest (138 vs 113 reports) as well as heart failure (179 vs 126 reports) were more common with dronedarone than amiodarone. Conclusion Dronedarone was associated with reports of ventricular arrhythmia, cardiac arrest, and torsade de pointes in clinical practice. Whether this observation accounts for the increased risk of fatal arrhythmia observed in a recent prospective trial requires further investigation.