Abstract and Introduction
Abstract
Aims: This post hoc analysis of the ATHENA trial (NCT00174785) assessed the effect of dronedarone on the estimated burden of atrial fibrillation (AF)/atrial flutter (AFL) progression to presumed permanent AF/AFL, and regression to sinus rhythm (SR), compared with placebo.
Methods and Results: The burden of AF/AFL was estimated by a modified Rosendaal method using available electrocardiograms (ECG). Cumulative incidence of permanent AF/AFL (defined as ≥6 months of AF/AFL until end of study) or permanent SR (defined as ≥6 months of SR until end of study) were calculated using Kaplan–Meier estimates. A log-rank test was used to assess statistical significance. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were estimated using a Cox model, adjusted for treatment group. Of the 4439 patients included in this analysis, 2208 received dronedarone, and 2231 placebo. Baseline and clinical characteristics were well balanced between groups. Overall, 304 (13.8%) dronedarone-treated patients progressed to permanent AF/AFL compared with 455 (20.4%) treated with placebo (P < 0.0001). Compared with those receiving placebo, patients receiving dronedarone had a lower cumulative incidence of permanent AF/AFL (log-rank P < 0.001; HR: 0.65; 95% CI: 0.56–0.75), a higher cumulative incidence of permanent SR (log-rank P < 0.001; HR: 1.19; 95% CI: 1.09–1.29), and a lower estimated AF/AFL burden over time (P < 0.01 from Day 14 to Month 21).
Conclusion: These results suggest that dronedarone could be a useful antiarrhythmic drug for early rhythm control due to less AF/AFL progression and more regression to SR vs. placebo, potentially reflecting reverse remodeling.
Clinical Trial Registration: NCT00174785
Graphical Abstract
Introduction
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with increased risk for stroke, heart failure, and cardiovascular death.[1–3] AF is a progressive arrhythmia that can advance from paroxysmal (duration ≤7 days) to persistent (duration >7 days without spontaneous conversion to sinus rhythm [SR]) or to permanent AF.[4,5] Results of a systematic review of use of AF ablation showed that in general population studies, progression to more persistent or permanent forms of AF occurred in 10%–20% of people with paroxysmal AF within 1 year of follow-up.[6] Progression over time to more persistent forms of AF is associated with increased disease burden, hospitalization rates, and increased mortality[4,7,8] and is related to structural and atrial electrical remodeling.[9,10] The findings of several studies support the use of rhythm control in people with AF to slow disease progression and improve cardiovascular outcomes.[11,12] Observational studies have shown that patients with non-permanent AF who received rhythm control were less likely to progress to permanent AF compared with those who received only rate control therapy,[13] and that early rhythm control is associated with a lower risk of adverse cardiovascular outcomes.[14] In the ATHENA trial, in which patients with paroxysmal or persistent AF were enrolled, treatment with dronedarone was associated with a significant reduction in the incidence of the primary composite endpoint of first cardiovascular hospitalization or death due to any cause compared with placebo.[15] Additionally, in a post hoc analysis of the ATHENA population, dronedarone demonstrated efficacy vs. placebo regardless of duration of AF/atrial flutter (AFL), but was more robust in those with short (<3 months) or intermediate (3 to <24 months) AF/AFL history compared with those with an AF/AFL history ≥24 months.[16] In the current post hoc analysis of ATHENA, we hypothesized that (i) there is a lower AF/AFL burden over time in patients receiving dronedarone compared with placebo, and (ii) there is less AF progression and more AF regression in dronedarone-treated vs. placebo-treated patients.
Europace. 2023;25(3):845-854. © 2023 Oxford University Press
Copyright 2007 European Heart Rhythm Association of the European Society of Cardiology (ESC). Published by Oxford University Press. All rights reserved.