February 12, 2009 - Sanofi-aventis said yesterday the ATHENA trial was published in the New England Journal of Medicine, which shows its drug Multaq (dronedarone), in addition to standard therapy, significantly reduced the risk of first cardiovascular hospitalization or death by 24 percent in patients with atrial fibrillation (AF)/atrial flutter (AFL) or a recent history of these conditions.
Atrial fibrillation is the leading cause of hospitalization for arrhythmia in the U.S.(1) and represents one-third of hospitalizations for arrhythmia in Europe(2). Hospitalization due to AF has increased dramatically (two-to-three fold) in recent years in the U.S.(1). Atrial fibrillation is a complex disease that increases the risk of stroke up to five-fold(3), worsens the prognosis of patients with cardiovascular risk factors4 and that doubles the risk of mortality(5).
The authors’ findings, as reported in the New England Journal of Medicine, showed a significant decrease in the risk of cardiovascular death by 29 percent in patients with AF. Multaq significantly decreased the risk of arrhythmic death by 45 percent and there were numerically fewer deaths (16 percent) from any cause in the dronedarone group compared to placebo. First cardiovascular hospitalization was reduced by 26 percent in the dronedarone group.
“The ATHENA trial is the first trial to show a reduction in the incidence of cardiovascular hospitalization or death in patients taking an anti-arrhythmic drug for atrial fibrillation” said Dr. Stefan H. Hohnloser J.W., Goethe University’s Division of Clinical Electrophysiology, Frankfurt, Germany, principal investigator of the ATHENA study.
Reported significant adverse events in the Multaq arm vs. placebo arm included diarrhea (9.7 vs. 6.2 percent), nausea (5.3 vs. 3.1 percent), bradycardia (3.5 vs. 1.2 percent), QT-interval prolongation (1.7 vs. 0.6 percent); skin disorders (10.3 vs. 7.6 percent) consisting mainly of rash, and an increase in blood creatinine (4.7 vs. 1.3 percent). There was no difference in permanent study drug discontinuation between Multaq and placebo (30.2 percent vs. 30.8 percent).
Dr. Stuart J. Connolly, Director of the division of cardiology at McMaster University, Ontario, Canada and co-principal investigator of the ATHENA trial said, “The clinical benefits observed with dronedarone in ATHENA occurred without a significantly higher rate of thyroid or pulmonary disorders compared with placebo reported within the study period.”
The ATHENA study is the only double-blind, antiarrhythmic study in patients with AF that assesses morbidity-mortality. The study was conducted at 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 factors) or below 75 years of age with at least one additional cardiovascular risk factor (hypertension, diabetes, previous ischemic cerebrovascular event, left atrium size greater than 50 mm or left ventricular ejection fraction lower than 40 percent). Patients with recently decompensated heart failure or in New York Heart Association (NYHA) class IV were excluded. Patients were randomized to receive dronedarone 400 mg BID or placebo, with a mean follow-up of 21 months.
The ATHENA study objectives were designed to show a potential benefit of dronedarone on the primary composite endpoint of all-cause mortality combined with cardiovascular hospitalization compared with 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.
(1) Singh SN et al. J Am Coll Cardiol. 2006;48:721-730
(2) Fuster V et al. ACC/AHA/ESC Guidelines. European Heart Journal 2006;27:1979–2030
(3) Wolf et al. Stroke. 1991;22:983-988.
(4) Wachtell K et al. J Am Coll Cardiol. 2005;45:712-719.
(5) Benjamin EJ et al. Circulation. 1998;98:946-952.
For more information: www.sanofi-aventis.us