Frequently Asked Questions

Atrial fibrillation (AF) is a frequent supraventricular tachyarrhythmia characterised by uncoordinated atrial activation with consequent deterioration of atrial mechanical function. AF can cause mainly palpitations, dyspnea, and fatigue. Atrial fibrillation (AF) currently represents a major economic burden for society. 70 percent of the annual cost of AF management is driven by inpatient care and interventional procedures. Hospitalisations for AF have increased dramatically (2- to 3-fold) in recent years. AF hospitalisations now represent a third of all hospitalisations for arrhythmia and mortality. AF affects nearly seven million people in the European Union and the United States.

AF is increasingly frequent with advancing age, caused by age-related changes in the heart or by an underlying cardiovascular disease. AF increases the risk of stroke five-fold and heart failure two- to three-fold. AF also doubles the risk of mortality and is an independent risk factor for sudden cardiac death.
 
Without appropriate management, AF can lead to serious complications such as stroke and congestive heart failure. Successful management of AF should also aim at further reducing CV morbidity and mortality.

The prevalence of AF is increasing with age. In addition, the majority of AF cases occur in a context of pre-existing cardiovascular disease, such as hypertension, coronary artery disease, valvular disorder, and congestive heart failure. Other medical conditions that can cause AF include congenital abnormalities, obesity, diabetes, and hyperthyroidism. AF can also be caused by environmental factors such as smoking, excessive alcohol consumption, caffeine and stress.

Some patients may be asymptomatic. However, in the great majority of patients, AF presents with a wide range of symptoms such as:
• Palpitations
• Weakness or tiredness
• Dyspnea, chest pain
• Dizziness or light-headedness
• Syncope
• Decrease in exercise performance (such as climbing stairs)

AF is a major cause of morbidity and mortality, increasing the risk of death, congestive heart failure and embolic phenomena, including stroke.
• The mortality rate of patients with AF is about double that of patients with normal sinus rhythm and is linked to the severity of underlying heart disease
• AF aggravates heart failure and in turn heart failure promotes AF
• AF is associated with an increase in the rate of ischemic strokes with 1 in every 6 strokes occurring in a patient with AF.

The diagnosis of AF is based on history and clinical examination, and confirmed by a standard ECG recording, generally sufficient to establish the diagnosis. Holter monitoring, transtelephonic or telemetric recordings may be necessary to confirm the arrhythmia.

AF is a potentially serious disturbance of the heart rhythm that occurs in about more than 7 million people worldwide. This number is expected to double within the next 20 years as the number of elderly people increase. The disorder may be even more common than can be detected because patients may experience AF episodes that either do not cause symptoms or are not documented during their visits to the doctor.

Dronedarone (brand name Multaq®) is an investigational compound developed by sanofi-aventis for the reduction in risk of cardiovascular hospitalisation or death in patients with atrial fibrillation/atrial flutter or with history of atrial fibrillation/atrial flutter. Dronedarone blocks calcium, potassium and sodium channels and has antiadrenergic effects and does not contain iodine.

Dronedarone has been approved under the brand name Multaq® by the US Food and Drug Administration on July 1, 2009 and by Health Canada on August 12, 2009. A registration dossier is currently under regulatory review by the European Medicines Agency (EMEA).

Dronedarone is a novel drug with multi-factorial mode of action that provides for the first time for an anti-arrhythmic drug a significant reduction of the risk for cardiovascular hospitalisation or death in patients with AF/AFL, with significant reduction of cardiovascular deaths. Dronedarone also showed a favourable safety profile with a low risk for of pro-arrhythmia or organ toxicity.

When compared with placebo, a slightly higher incidence of gastrointestinal disorders (mainly diarrhoea), increased blood creatinine (with no evidence of renal toxicity) and cutaneous disorders (mainly rash) have been observed.

We cannot speculate on the final labelling until full assessment is done by the Regulatory Agencies. Product labelling will be developed based upon all available clinical data including the ATHENA results and will be defined by the health authorities.

Since dronedarone is under FDA and EMEA review, it would be premature to comment on specifics such as possible cost, level of reimbursement and other details.

We can’t speculate on the business decisions of other companies, but the development of drugs for the treatment of AF is extremely complex and led to clinical development discontinuations. Sanofi-aventis continues to be committed to the development of innovative therapies that improve clinical outcomes and provide new hope to more patients burdened with a wide range of cardiovascular diseases.

ATHENA stands for 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. It is a double-blind, placebo-controlled morbidity and mortality study in patients with Atrial Fibrillation/Flutter (AF/AFL) and additional cardiovascular risk factors. This is the largest study (4,628 patients) ever conducted in AF/AFL, and the first time a drug for AF was tested in a study for clinical outcomes (instead of the conventional surrogate endpoint of AF/AFL recurrences).

ATHENA is the first and only AF/AFL clinical drug trial that showed a reduction of cardiovascular hospitalisations or death from any cause by a statistically significant 24 percent (p=0.00000002). This positions it as a landmark trial. ATHENA has been published on February 12th 2009. (Hohnloser SH et al. N Engl J Med 2009;360:668-78).

ATHENA shows a reduction in the need for cardiovascular hospitalisations with potential impact on more than 6 million AF/AFL patients worldwide in providing a better quality of life.
Dronedarone is the first drug that has demonstrated a significant decrease in cardiovascular mortality, including cardiac arrhythmic death, in AF/AFL patients. In addition, ATHENA provided extensive confirmation of the overall good safety and tolerability profile of dronedarone, associated with a low risk of proarrhythmia or organ toxicity.

If approved, dronedarone would set a new step forward for evaluating the therapeutic effect of a drug for the treatment of patients with atrial fibrillation, and a new advance in the management of AF, overcoming the rhythm versus rate historical debate.