More on AF

Dronedarone is a novel anti-arrhythmic drug which has been studied in a comprehensive clinical development program involving over 7,000 patients^1,2,3,4,5,6. This program included five placebo controlled studies in patients with atrial fibrillation (AF)ⁱ or atrial flutter (AFL)ⁱ called EURIDIS², ADONIS², ERATO³ and ATHENA⁶; the DIONYSOS⁴ trial, a comparative trial vs amiodarone; and the ANDROMEDA⁵ trial, a placebo controlled study in heart failure patients with a recent hospitalization for decompensated systolic heart failure. Almost 4,000 patients received dronedarone during the clinical development program.

• The landmark ATHENA⁶ trial, was the largest anti-arrhythmic drug trial ever conducted in patients with AF/AFL, involving 4,628 patients and a follow-up of 30 months. In this trial, dronedarone, on top of standard therapy, significantly reduced cardiovascular hospitalization or death by 24 percent when compared to placebo, meeting the study’s primary endpointⁱ. This reduction was generally consistent across study subgroups based on baseline characteristics or medications.

• The most common adverse reactions were diarrhea, nausea, vomiting, abdominal pain, asthenia (weakness) and skin rash⁶.

• Dronedarone has a convenient fixed dose regimen of twice daily 400 mg tablets to be taken with morning and evening meals. Treatment with dronedarone does not require a loading dose and can be initiated in an outpatient setting with minimal monitoring⁷.

• 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).

• In the U.S. dronedarone is indicated⁸ to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent AF or AFL, with a recent episode of AF/AFL and associated cardiovascular risk factors, who are in sinus rhythmⁱ or who will be cardioverted. Associated cardiovascular risk factors include age over 70 years, hypertension, diabetes, prior cerebrovascular accident, left atrial diameter ≥50 mm or left ventricular ejection fraction [LVEF] <40%. In Canada dronedarone is indicated⁹ for the treatment of patients with a history of, or current AF to reduce their risk of cardiovascular hospitalization due to this condition.

• In the U.S. and in Canada, initiation of dronedarone treatment is contraindicated in patients with severe heart failure (New York Heart Association – NYHA class IV). Dronedarone is also contraindicated in the US for NYHA Class II – III heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic. In Canada, initiation is contraindicated in other unstable hemodynamic conditions and dronedarone should be used with caution in patients with moderate congestive heart failureⁱ (NYHA Stage III).
   
• Dronedarone was discovered and developed by sanofi-aventis, it represents one of the few therapeutic advances for AF and AFL management in the last 20 years. Dronedarone’s broad clinical development program illustrates sanofi-aventis’ ongoing commitment to provide patients, physicians and public health stakeholders with new options in a therapeutic areas where there are unmet medical needs.

References :

1. Touboul P, Brugada J, Capucci A, Crijns HJ, Edvardsson N, Hohnloser SH: Dronedarone for prevention of atrial fibrillation: A dose-ranging study. Eur Heart J 2003;24:1481-1487.
2. Singh BN, Connolly SJ, Crijns HJ, Roy D, Kowey PR, Capucci A, Radzik D, Aliot EM, Hohnloser SH; EURIDIS and ADONIS Investigators. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N Engl J Med. 2007 Sep 6;357(10):987-99.
3. Davy JM. Herold M et al. Dronedarone for the control of ventricular rate in permanent atrial fibrillationⁱ: the Efficacy and safety of dRonedArone for the cOntrol of ventricular rate during atrial fibrillation (ERATO) study. Am Heart J. 2008 Sep;156(3):527.e1-9.
4. Sanofi-aventis [Internet]. Paris. Sanofi-aventis [© Sanofi-aventis 2004-2009 - Update: March 18, 2009]. DIONYSOS study results showed the respective profiles of dronedarone and amiodarone [update December 23 2008; cited July 3 2009]. Available from http://en.sanofi-aventis.com/binaries/20081223_dionysos
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5. L. . Køber, C. Torp-Pedersen, J.J.V. McMurray, O. Gøtzsche, S. Lévy, H. Crijns, J. Amlie, J. Carlsen, for the Dronedarone Study Group. Increased Mortality after Dronedarone Therapy for Severe Heart Failure. New Eng. J. Med. 2008;358:2678-2687.
6. Hohnloser SH, Crijns HJ, van Eickels M, Gaudin C, Page RL, Torp-Pedersen C, Connolly SJ; ATHENA Investigators. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med. 2009;360(7):668-78.
7. Sanofi-aventis data on file
8. Food and Drug Administration [Internet]. Silver Spring, MD: FDA [updated July 2 2009; cited July 3 2009] FDA Approves Multaq to treat heart rhythm disorder [about one screen]. Available from http://www.fda.gov/NewsEvents/Newsroom/
PressAnnouncements/ucm170276.htm
9. Sanofi-aventis data on file