Impact of dronedarone on hospitalization burden in patients with atrial fibrillation: results from the ATHENA study

Abstract

Aims: Cardiovascular (CV) hospitalization is a predictor of CV mortality and has a negative impact on patients' quality of life. The primary endpoint of A placebo-controlled, double-blind, parallel-arm Trial to assess the efficacy of dronedarone 400 mg bid for the prevention of cardiovascular Hospitalization or death from any cause in patiENTs with Atrial fibrillation/atrial flutter (ATHENA), a composite of first CV hospitalization or death from any cause, was significantly reduced by dronedarone. This post hoc analysis evaluated the secondary endpoint of CV hospitalization and the clinical benefit of dronedarone on the number and duration of CV hospitalizations in patients with atrial fibrillation (AF).

Methods and results: ATHENA was a double-blind, parallel group study in 4628 patients with a history of paroxysmal/persistent AF and additional risk factors, treated with placebo or dronedarone. Dronedarone treatment significantly reduced the risk of first CV hospitalization (P < 0.0001 vs. placebo), while the risk of first non-CV hospitalization was similar in both groups (P = 0.77). About half of the CV hospitalizations were AF-related, with a median duration of hospital stay of four nights. The risk of any hospitalization for AF [hazard ratio (95% confidence interval) 0.626 (0.546-0.719)] and duration of hospital stay were significantly reduced by dronedarone (P < 0.0001 vs. placebo). Dronedarone treatment reduced total hospitalizations for acute coronary syndrome (P = 0.0105) and the time between the first AF/atrial flutter recurrence and CV hospitalization/death (P = 0.0048). Hospitalization burden was significantly reduced across all levels of care (P < 0.05). Cumulative incidence data indicated that the effects of dronedarone persisted for at least 24 months.

Conclusion: Dronedarone reduced the risk for CV hospitalization and the total hospitalization burden in this patient group. The trial is registered under ClinicalTrials.gov #NCT 00174785.

Trial registration: ClinicalTrials.gov NCT00174785.

Figures

Figure 1

Kaplan–Meier cumulative incidence curves of time from randomization to first hospitalization for the intention-to-treat population. (A) Cardiovascular hospitalization; (B) non-cardiovascular hospitalization; (C) hospitalization for atrial fibrillation and other supraventricular disorders; (D) non-atrial fibrillation/atrial flutter hospitalization.

Figure 2

Kaplan–Meier cumulative incidence curves of time from first atrial fibrillation/atrial flutter recurrence (based on electrocardiograms and cardioversion) to first cardiovascular hospitalization during the on-study period. Data are for all randomized patients with a first atrial fibrillation/atrial flutter recurrence and without presence of atrial fibrillation/atrial flutter as per stratification factor.

Figure 3

Incidence of cardiovascular and non-cardiovascular hospitalizations. (A) Summary of Nelson–Aalen cumulative incidence curves of all cardiovascular and non-cardiovascular hospitalizations during the on-study period (intention-to-treat population); (B) curve and summary of cumulative incidence difference between each time point for all cardiovascular and non-cardiovascular hospitalizations during the on-study period (intention-to-treat population).

Figure 4

Hazard ratio (dronedarone 400 mg bd vs. placebo) estimates with confidence intervals according to region. (A) Primary endpoint (first cardiovascular hospitalization or death from any cause); (B) cardiovascular hospitalization. Data are for all randomized patients. aDetermined from Cox regression model. bP values are for interaction between regions and treatment based on Cox regression model.