Dronedarone Reduced Hospitalization In Atrial Fibrillation Patients
New data from the landmark ATHENA trial showed that dronedarone significantly reduced the incidence and total duration of hospital stays among patients with atrial fibrillation/atrial flutter (AF/AFL). This post-hoc analysis was presented at the 2008 American Heart Association Scientific Sessions in New Orleans, Louisiana.
In this new analysis, dronedarone significantly reduced the total number of hospital days by 28 percent (p<0.001) versus placebo (9,995 days vs. 13,986 days), and decreased by 35 percent (p<0.001) the total length of time spent in hospital for cardiovascular reasons (5,875 days vs. 9,073 days).
In addition to the demonstrated reduction of AF-related hospitalization by 37 percent (p<0.001), dronedarone reduced the incidence of first non-AF related CV hospitalization (e.g. myocardial infarction or unstable angina by 14 percent (p=0.016). Dronedarone did not increase the incidence of non-cardiovascular hospitalizations in comparison to the placebo arm.
"The incidence of AF-related hospital admissions has dramatically increased in recent years, and therapeutic solutions to reduce this burden are needed," said Dr. Christian Torp-Pedersen from the Gentofte University Hospital, Copenhagen, Denmark and a member of the steering committee of the ATHENA study. "These new ATHENA data showed that, for the first time, an anti-arrhythmic drug significantly and consistently reduced hospitalization incidence and duration, which led to a substantial reduction of total hospitalization burden in this patient population."
A second post-hoc analysis from ATHENA also presented during the AHA, confirmed the rhythm and rate controlling properties of dronedarone, previously demonstrated in lower risk populations studied in the EURIDIS(1), ADONIS and ERATO(2) trials. This analysis showed that dronedarone reduced the incidence of first AF recurrence by 25 percent in patients in sinus rhythm at study initiation (p<0.001), and the incidence of first electrical cardioversion by 31 percent (p<0.001), compared with placebo.
Dronedarone also decreased mean heart rate during atrial fibrillation to 78 beats per minute, compared with 87 for placebo (p<0.001). Fewer patients developed permanent atrial fibrillation during the study in the dronedarone group - 178 patients (7.7%) compared with 295 patients (12.7%) in the placebo arm (p<0.001). In these patients, the non-significant reduction of CV hospitalization or death was 26% lower for those receiving dronedarone (p=0.096). These results are consistent with the overall study results.
"This study demonstrates both significant rhythm and rate controlling properties of dronedarone in the ATHENA population, which consisted of higher-risk patients with atrial fibrillation," added Dr. Richard Page, Professor and Head of the Division of Cardiology at the University of Washington School of Medicine, Seattle, USA and a member of the steering committee of the ATHENA study. "It is intriguing that there was a trend toward reduction of the primary endpoint of cardiovascular hospitalization or death even in patients with permanent AF, suggesting that the benefit of dronedarone may not only be linked to arrhythmia control."
The most frequently reported adverse events of dronedarone vs. placebo in the ATHENA trial were gastrointestinal effects (26% vs. 22%), skin disorders (10% vs. 8%, mainly rash) and mild increase in blood creatinine (4.7% vs. 1%) due to inhibition of tubular secretion of creatinine in the kidneys. The mechanism of blood creatinine increase was well defined in a separate study of healthy volunteers and is not indicative of renal toxicity. In the ATHENA trial, compared to placebo, dronedarone showed a low risk of pro-arrhythmia and no excess of hospitalizations for congestive heart failure. There was a similar rate of study drug discontinuation between the 2 study groups.