Further Analysis From The ATHENA Study Showed That Multaq® (dronedarone) Reduced The Risk Of Stroke In Patients With Atrial Fibrillation

Main Category: Cardiovascular / Cardiology
Also Included In: Stroke;  Clinical Trials / Drug Trials
Article Date: 03 Sep 2008 - 3:00 PDT

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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 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 dronedarone decreased the risk of stroke (ischemic or haemorrhagic) compared to placebo by 34% (46/2301 vs 70/2327 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 dronedarone was incremental to background anti-thrombotic therapy like oral anticoagulants and / or anti-platelet agents.

"ATHENA is a landmark trial, 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 dronedarone beyond its pure rhythm and rate-controlling effects," said Professor Stuart Connolly, Mc Master University, Department of Cardiology, Hamilton Canada, co-principal investigator of the ATHENA study.

The most frequently reported adverse events of dronedarone 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%) 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, dronedarone 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 2 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 dronedarone 400 mg BID or placebo, with a maximum follow-up of 30 months.

The ATHENA study objectives were to show a potential benefit of dronedarone 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 dronedarone in atrial fibrillation or atrial flutter patients in reducing major cardiovascular complications like stroke, which is a leading cause of cardiovascular hospitalization or death in this patient population.

About Multaq® (dronedarone)

Dronedarone is an investigational treatment and the only anti-arrhythmic drug (AAD) to have shown, as seen in ATHENA, a significant reduction in morbidity and mortality in atrial fibrillation /atrial flutter patients compared with baseline treatment. In the same study dronedarone also demonstrated a favourable safety profile as evidenced by a low incidence of pro-arrhythmia (including torsades de pointes) and extra-cardiac organ toxicity. Dronedarone, discovered and developed by sanofi-aventis, has been studied in a clinical development program including more than 7,000 patients. Dronedarone is one of the major therapeutic innovations for atrial fibrillation in the last twenty years.

Dronedarone 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). Dronedarone is not expected to be available for use in the NHS before September 2009.

About sanofi-aventis

Sanofi-aventis, a leading global pharmaceutical company, contributes to improving life by providing a broad offering of medicines, vaccines, and integrated healthcare solutions adapted to local needs and means. http://en.sanofi-aventis.com

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