Sep 3 2008
The results of a post-hoc analysis of the data from the ATHENA study were presented today 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 hospitalisations 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 haemorrhagic) 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 anti-platelet 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 a 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. In the ATHENA trial, compared to placebo, Multaq showed a low risk of pro-arrhythmia and no excess of hospitalisations for congestive heart failure. There was a similar rate of study drug discontinuation between the study groups.
About Atrial Fibrillation/Flutter and Stroke
Atrial Fibrillation (AF) is the most common cardiac arrhythmia in clinical practice and is one of the most important independent risk factors for stroke. Stroke is a major public health problem because this acute event often causes permanent neurological disabilities and death.
Atrial fibrillation increases the risk of stroke by up to 5 times. It also is responsible for 15-20% of all strokes, which if caused by AF, are 2.2 times more likely to leave patients bedridden.
Atrial fibrillation is a major cause of hospitalisation and mortality and affects about 2.5 million people in the USA and 4.5 million people in the European Union. The Atrial Fibrillation Foundation expects the number of patients with AF to double in the next 20 years. Without appropriate management, atrial fibrillation can lead to serious complications, such as stroke and congestive heart failure.
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 hospitalisation 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, adverse events leading to study drug discontinuation.
The ATHENA stroke post-hoc analysis on a 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, which is a leading cause of cardiovascular hospitalizations or death in this patient population.
About Multaq (dronedarone)
Multaq is an investigational treatment and the only anti-arrhythmic drug (AAD) to have shown a significant reduction in morbidity and mortality in atrial fibrillation/atrial flutter patients with a favourable safety profile as evidenced by a low incidence of pro-arrhythmia (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 is one of the major therapeutic innovations in the field of atrial fibrillation in the last twenty years.
Multaq has been granted a priority review by the U.S. Food and Drug Administration (FDA) and a registration dossier is also under regulatory review by the European Medicines Agency (EMEA).
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