Effect of dronedarone on clinical end points in patients with atrial fibrillation and coronary heart disease: insights from the ATHENA trial.

AIMS: This study aimed to assess safety and cardiovascular outcomes of dronedarone in patients with paroxysmal or persistent atrial fibrillation (AF) with coronary heart disease (CHD). Coronary heart disease is prevalent among AF patients and limits antiarrhythmic drug use because of their potentially life-threatening ventricular proarrhythmic effects.

METHODS AND RESULTS: This post hoc analysis evaluated 1405 patients with paroxysmal or persistent AF and CHD from the ATHENA trial. Follow-up lasted 2.5 years, during which patients received either dronedarone (400 mg twice daily) or a double-blind matching placebo. Primary outcome was time to first cardiovascular hospitalization or death due to any cause. Secondary end points included first hospitalization due to cardiovascular events. The primary outcome occurred in 350 of 737 (47%) placebo patients vs. 252 of 668 (38%) dronedarone patients [hazard ratio (HR) = 0.73; 95% confidence interval (CI) = 0.62-0.86; P = 0.0002] without a significant increase in number of adverse events. In addition, 42 of 668 patients receiving dronedarone suffered from a first acute coronary syndrome compared with 67 of 737 patients from the placebo group (HR = 0.67; 95% CI = 0.46-0.99; P = 0.04).

CONCLUSION: In this post hoc analysis, dronedarone on top of standard care in AF patients with CHD reduced cardiovascular hospitalization or death similar to that in the overall ATHENA population, and reduced a first acute coronary syndrome. Importantly, the safety profile in this subpopulation was also similar to that of the overall ATHENA population, with no excess in proarrhythmias. The mechanism of the cardiovascular protective effects is unclear and warrants further investigation.