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

^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 The burden of AF/AFL was estimated by a modified Rosendaal method using available electrocardiograms (ECG). and ^results 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. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Graphical Abstract Effect of dronedarone vs. placebo on atrial fibrillation progression: a post hoc analysis from the ATHENA trial Conclusion These results suggest that dronedarone could be a useful antiarrhythmic drug for early rhythm control because there was less AF/AFL progression and more regression to SR versus placebo, potentially reflecting reverse remodeling OBJECTIVE ^METHODS_{To assess whether dronedarone vs placebo} Cumulative incidence of presumed permanent _affects: AF/AFL or permanent SR was calculated using • Progression of AF/AFL to more persistent forms ^the_statistical^complement_significance^{of Kaplan–Meier}_{assessed by}^estimates,_{log-rank test}^with • ^Regression_{regression to}^of_permanent^{AF/AFL, measured}_SR^by AF/AFL _Rosendaal burden _method, was _based estimated _{on the} using _presence a modified • AF/AFL burden, defined as the amount of or absence of AF/AFL assessed by ECG at time in AF/AFL each visit KEY RESULTS Progressed to permanent AF/AFL Cumulative Incidence Curves for Regression to Permanent SR 13.8% Permanent _AF/AFL^20.4% Permanent _AF/AFL¹⁰⁰_Placebo Dronedarone Log-rank P<0.001 Nonpermanent ^{Dronedarone Placebo} Nonpermanent ⁸⁰ AF/AFL AF/AFL 86.2% 79.6% 60 A total of 304 (13.8%) dronedarone-treated patients progressed to permanent AF/AFL compared with 455 (20.4%) ⁴⁰ who received placebo (P<0.0001) Regression to permanent SR 20 _48.0% 54.2% _{0 0} 60 120 180 240 300 360 420 480 540 600 660 720 Permanent SR Permanent SR _Time (days) Dronedarone Placebo Not in ^{SR Not} in ^SR Cumulative incidence of permanent SR over time was significantly 52.0% 45.8% higher in those receiving dronedarone vs placebo (HR; 1.19; 95% CI 1.09-1.29); patients treated with dronedarone were A total of 1149 (52.0%) dronedarone-treated patients achieved permanent ^19% more likely to improve to permanent SR over time SR compared with 1021 (45.8%) who received placebo (P=0.006) Mean Estimated AF/AFL Burden (%) Over Time Using Modified Cumulative Incidence Curves for Progression to Permanent AF/AFL _* Rosendaal Method ³⁰ Placebo Dronedarone Log-rank P<0.001 ₈₀ ** *** 70 *** ^{20 ***} *** ^** *** _{*** *} 60 10 ₅₀ Placebo 40 Dronedarone 0 0 60 120 180 240 300 360 420 480 540 600 660 720 _D7 D14 M1 M3 M6 M12 M15 M18 M21 M24 Time (days) ±2D ±5D ±7D ±14D ±14D ±14D ±14D ±14D ±14D ±14D Cumulative incidence over time of permanent AF/AFL was significantly Analysis Visit lower in dronedarone-treated patients (HR; 0.65; 95% CI 0.56-0.75); ^*P < 0.05; **P < 0.001; ***P < 0.0001. patients treated with dronedarone were 35% less likely to Estimated AF/AFL burden over time was lower in progress to permanent AF/AFL over time dronedarone- vs placebo-treated patients AF, atrial fibrillation; AFL, atrial flutter; CI, confidence interval; D, day; ECG, electrocardiogram; HR, hazard ratio; M, month; SR, sinus rhythm.