Abstract 4097: Rhythm- and Rate-Controlling Effects of Dronedarone in Patients with Atrial Fibrillation: Insights From the ATHENA Trial
Background: Dronedarone (D) is a new multi-channel blocking drug for the treatment of patients with paroxysmal or persistent atrial fibrillation (AF) or flutter (AFL). ATHENA is a double-blind, placebo (P) controlled randomized study of dronedarone (400 mg bid) comprising 4628 medium- to high-risk patients (pts) with AF/AFL. D treatment was associated with a highly significant reduction in the primary outcome of the trial, time to first cardiovascular hospitalization or death from any cause. Rates of clinically important adverse events were comparable in both groups. This analysis evaluates the rhythm- and rate-controlling properties of D in detail.
Methods: In ATHENA, pts were scheduled for regular office visits with 12-lead ECGs taken at each visit. All ECG tracings available were classified for AF/AFL or sinus rhythm. In all AF/AFL recordings, ventricular rate was determined. Pts with AF/AFL in every post-baseline ECG were classified as having permanent AF/AFL. All electrical cardioversions were prospectively documented.
Results: A total of 2327 pts were randomized to P, 2301 to D. Mean age was 72 years, 47% were female, and 60% had structural heart disease. Mean follow-up was 21 months. In the D group, 339 (14.7%) had at least 1 electrical cardioversion compared to 481 (20.7%) in the P group (hazard ratio (HR): 0.68, 95% CI: 0.60 – 0.79, p<0.001). Of 586 P pts with AF/AFL at randomization, 195 underwent electrical cardioversion compared to 151 of 569 D pts (HR: 0.76, 95% CI: 0.61– 0.94, p=0.01). The likelihood of permanent AF/AFL was lower with D (179 pts) compared to P (294 pts) (p<0.001). The median time to first AF/AFL recurrence of pts in sinus rhythm at baseline was prolonged from 498 days in P pts to 737 days in D pts (HR 0.75, 95% CI 0.68 – 0.82; p<0.001). A total of 4596 ECG recordings in P pts and 3274 in D pts documented AF/AFL. The use of background rate-controlling medications (beta-blocker, calcium channel-blocker, digoxin) were equally distributed in both treatment groups. Median heart rate during AF/AFL was 84 bpm vs 75 bpm in the P and the D groups, respectively (p<0.001).
Conclusion: D exhibits both, rhythm- and rate-controlling properties in AF/AFL pts. These effects are likely to contribute to the reduction of important clinical outcomes observed in ATHENA.