Dronedarone as early rhythm control: post-hoc analysis of the ATHENA trial using EAST-AFNET4 criteria

Abstract

Abstract Introduction The EAST-AFNET4 study found that early, systematic rhythm control reduced cardiovascular (CV) outcomes in patients with early atrial fibrillation/atrial flutter (AF) of ≤12 months compared to guideline-recommended usual care. Purpose This post-hoc analysis aimed to assess whether antiarrhythmic drug therapy alone (i.e. dronedarone 400 mg BID) improved CV outcomes compared to placebo in patients with early AF in the ATHENA trial (NCT00174785; Ref 2) applying the EAST-AFNET4 criteria. Methods All patients in the randomised, placebo-controlled ATHENA trial with ≥2 CV conditions as defined in the EAST-AFNET 4 inclusion criteria and known AF duration at baseline were identified. Patients were split into early AF (≤12 months duration) and late AF (>12 months duration) subgroups. Outcomes were collected over a mean follow-up of 21 months and included a composite of CV death, stroke, or hospitalisation with worsening of heart failure or acute coronary syndrome; nights spent in hospital per year; and a safety composite endpoint comprising death, stroke, or pre-specified serious adverse events. All analyses were conducted in the intention-to-treat population. Results Dronedarone treatment was associated with significantly (p=0.014) fewer CV events vs placebo in patients with early AF (Fig 1). There was no interaction with AF duration (p=0.64). Patients on dronedarone spent numerically fewer nights in hospital vs placebo in early (13.4 vs 14.0) and late AF (13.9 vs 16.3), with no treatment interaction between subgroups (p=NS). Dronedarone was associated with more sinus rhythm (SR) at 12 months vs placebo (early AF: 79.9% vs 70.3%; late AF: 60.6% vs 54.0%), and similar rates of SR at 24 months (early AF: 65.8% vs 65.7%; late AF: 54.7% vs 54.1%). For the safety composite endpoint, estimated events/patients were as follows for the early AF group (dronedarone: 153/135; placebo: 182/165) and the late AF group (dronedarone: 86/81; placebo: 95/89). Conclusions The clinical benefit of early rhythm control found in the EAST-AFNET4 trial can be replicated in this analysis of patients with early AF treated in the ATHENA trial comparing dronedarone to placebo. These data support the use of dronedarone as part of early rhythm control. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Sanofi