Further Analysis from the ATHENA Study Showed Multaq® (dronedarone) Reduced the Risk of Stroke in Patients with Atrial Fib

The results of a post-hoc analysis of the data from the ATHENA study were presented at the clinical trial update session of the European Society of Cardiology Congress 2008 in Munich, Germany. Previous results from the landmark ATHENA study have shown that the investigational medicine Multaq® (dronedarone) on top of standard therapy decreased the combined primary endpoint of the risk of cardiovascular hospitalizations or death from any cause by a statistically significant 24% (p=0.00000002) as compared to placebo. The ATHENA stroke post-hoc analysis on non-pre-specified secondary endpoints showed that Multaq® decreased the risk of stroke (ischemic or hemorrhagic) compared to placebo by 34% (46 vs. 70 stroke events respectively; p=0.027) in atrial fibrillation/atrial flutter patients adequately treated by standard therapy including antithrombotics. The significant reduction in stroke risk with Multaq® was incremental to background anti-thrombotic therapy like oral anticoagulants and/or antiplatelet agents. Similar to the ATHENA primary endpoint of CV hospitalizations or death, this effect appeared early and was maintained during the study follow-up (12 to 30 months). "ATHENA is a landmark trial that will lead to a paradigm shift in the management of atrial fibrillation as it is the first time that an anti-arrhythmic drug has shown a significant impact on cardiovascular outcomes. As stroke is one of the leading complications of atrial fibrillation, and a major cause of death and long-term disability, these new results demonstrate the unique profile of Multaq® beyond its pure rhythm and rate-controlling effects," said Professor Stuart Connolly, McMaster University, Department of Cardiology, Hamilton Canada, co-principal investigator of the ATHENA study. The most frequently reported adverse events of Multaq® vs. placebo in the ATHENA trial as seen in the pre-specified safety analysis, were gastrointestinal effects (26% vs. 22%), skin disorders (10% vs. 8%, mainly rash) and mild increase in blood creatinine (4.7% vs. 1%). The mechanism of blood creatinine increase was well defined in a separate study of healthy volunteers. In the ATHENA trial, compared to placebo, Multaq® showed a low risk of proarrhythmia and no excess of hospitalizations for congestive heart failure. There was a similar rate of study drug discontinuation between the two study groups. About the ATHENA Study The landmark ATHENA study is the only double-blind, anti-arrhythmic, morbidity-mortality study in patients with atrial fibrillation. It was conducted in more than 550 sites in 37 countries and enrolled a total of 4,628 patients. The patients studied in ATHENA were either 75 years of age or older (with or without cardiovascular risk factor) or above 70 years of age with at least one additional cardiovascular risk factor (hypertension, diabetes, previous cerebrovascular event, left atrium size greater than 50 mm or left ventricular ejection fraction lower than 40%). Patients were randomized to receive Multaq® 400 mg BID or placebo, with a maximum follow-up of 30 months. The ATHENA study objectives were to show a potential benefit of Multaq® on the primary composite endpoint of all-cause mortality combined with cardiovascular hospitalization as compared to placebo. The pre-specified secondary endpoints were death from any cause, cardiovascular death and hospitalization for cardiovascular reasons. The pre-specified safety endpoint was the incidence of treatment emergent adverse events (between first study drug intake and last study drug intake plus 10 days) including: all adverse events, serious adverse events, and adverse events leading to study drug discontinuation. The ATHENA stroke post-hoc analysis on non-pre-specified secondary endpoint was conducted in order to confirm the consistent benefit of Multaq in atrial fibrillation or atrial flutter patients in reducing major cardiovascular complications like stroke. About Multaq® (dronedarone) Multaq® is an investigational treatment and the only anti-arrhythmic drug to have shown a significant reduction in morbidity and mortality in atrial fibrillation/atrial flutter patients with a favorable safety profile as evidenced by a low incidence of proarrhythmia (including torsades de pointes) and extra-cardiac organ toxicity. Multaq®, discovered and developed by sanofi-aventis, has been studied in a clinical development program including more than 7,000 patients. Multaq® has been granted a priority review by the U.S. Food and Drug Administration and a registration dossier is also under regulatory review by the European Medicines Agency.