Effect of dronedarone versus placebo on atrial fibrillation progression: a post-hoc analysis from ATHENA trial

Abstract

Abstract Background Atrial fibrillation (AF) may progress over time, leading to greater AF burden. Data suggest that patients receiving rhythm control drugs are less likely to progress to more severe forms of AF vs those receiving a rate control strategy only. ATHENA (NCT00174785) demonstrated that dronedarone significantly decreased cardiovascular (CV) hospitalization and death [1], but it is unclear whether dronedarone affects progression of AF and atrial flutter (AFL). Purpose This post hoc analysis of ATHENA assessed (1) the effect of dronedarone on estimated AF/AFL burden, and (2) AF progression to presumed permanent AF/AFL or AF regression to sinus rhythm (SR). Methods AF/AFL burden was estimated using a modified Rosendaal method [2] based on status of all ECG assessments at each visit. Cumulative incidence of presumed permanent AF/AFL (defined as ≥6 months of AF/AFL until end of study) or preserved SR (≥6 months of SR until end of study) were calculated using the complement of Kaplan-Meier estimates. Log-rank test was used to assess statistical significance. Results Demographic characteristics in 2231 patients on placebo and 2208 on dronedarone were well balanced between groups. Overall, 304 (13.8%) dronedarone-treated patients progressed to presumed permanent AF/AFL compared with 455 (20.4%) treated with placebo. Patients progressing to presumed permanent AF/AFL tended to have larger left atrial diameters and lower left ventricular ejection fractions irrespective of treatment group. The cumulative incidence of presumed permanent AF/AFL was significantly lower in dronedarone-treated patients over time (log-rank p<0.0001; Figure 1). Estimated AF/AFL burden was lower in dronedarone-treated patients over time (Figure 2). Overall, 1149 (52.0%) dronedarone-treated patients had preserved SR compared with 1021 (45.8%) placebo-treated patients, and cumulative incidence of preserved SR was significantly higher in the dronedarone arm compared with the placebo arm (log-rank p<0.0001). Treatment-emergent adverse events were consistent with the findings in the main ATHENA analysis. Conclusions Dronedarone use was associated with fewer patients progressing to presumed permanent AF/AFL, more patients with AF/AFL regressing to preserved SR, and a lower estimated AF/AFL burden, suggesting a protective benefit against AF disease progression. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Sanofi