Meta-analysis of cardiovascular outcomes with dronedarone in patients with atrial fibrillation or heart failure

Dronedarone is a benzofuran derivative approved by the Food and Drug Administration to decrease the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF) and associated cardiovascular risk factors who are in sinus rhythm or will undergo cardioversion. There has been recent evidence to suggest that dronedarone may not have a favorable safety profile. We decided to evaluate all available evidence on the cardiovascular safety of this drug. A systematic search was made of the PubMed, CENTRAL, and EMBASE databases for randomized controlled trials from 1966 through 2011 comparing dronedarone to comparators in AF/heart failure. Intervention was dronedarone for AF for some studies and heart failure for others. Comparators included standard medical therapy and/or placebo and amiodarone for 1 study. Outcomes assessed were all-cause mortality, cardiovascular mortality, ventricular arrhythmias, embolic events, acute coronary syndrome, heart failure exacerbations, and hospitalization rates in the intervention versus comparator group at the end of ≥ 3 months of follow up with abstraction of data by 1 author. Seven randomized controlled trials were included in our analysis. Dronedarone use was associated with a trend toward worse all-cause and cardiovascular mortalities and increased heart failure exacerbations. It also showed numerically higher event rates for all other outcome events except acute coronary syndrome. Our pooled analysis showed increased all-cause and cardiovascular mortalities and increased heart failure exacerbations with use of dronedarone across a wide spectrum of populations. In conclusion, we recommend exercising caution using dronedarone, especially in patients with cardiovascular risk factors.