Neue Medikamente zur Behandlung von Vorhofflimmern – gibt es eine Alternative zu Amiodaron?

Abstract

Atrial fibrillation is the most common arrhythmia requiring treatment interventions with a high prevalence in elderly patients. In elderly asymptomatic patients rate control is the therapy of choice, whereas in symptomatic patients antiarrhythmic therapy or pulmonary vein isolation would be preferred. However, many currently used antiarrhythmic drugs have limited efficacy and cause irreversible organ toxicity. Amiodarone is the most potent antiarrhythmic agent for the treatment of atrial fibrillation. However, its use is limited by toxic effects on thyroid, lungs, liver, cornea, skin, and peripheral nerves. Thus compound development is more focused on congeners of Amiodarone. Dronedarone is a noniodinated benzofuran with similar electrophysiological effects compared to Amiodarone. Other compounds are under investigation. This review summarizes preclinical and clinical findings of these agents.

Literatur

• 1 Laughlin J C, Kowey P R. Dronedarone: a new treatment for atrial fibrillation.  J Cardiovasc Electrophysiol. 2008;  19 1220-1226
• 2 Verma A. Atrial-fibrillation ablation should be considered first-line therapy for some patients.  Curr Opin Cardiol. 2008;  23 1-8
• 3 Singh B N. Amiodarone as paradigm for developing new drugs for atrial fibrillation.  J Cardiovasc Pharmacol. 2008;  52 300-305
• 4 Doggrell S A, Hancox J C. Dronedarone: an amiodarone analogue.  Expert Opin Investig Drugs. 2004;  13 415-426
• 5 Christ T, Wettwer E, Voigt N. et al . Pathology-specific effects of the IKur/Ito/IK,ACh blocker AVE0118 on ion channels in human chronic atrial fibrillation.  Br J Pharmacol. 2008;  154 1619-1630
• 6 Schmitt J, Ehrlich J R, Hohnloser S H. New antiarrhythmic drugs for the treatment of atrial fibrillation.  Herz. 2008;  33 562-567
• 7 Gautier P, Serre M, Cosnier-Pucheu S. et al . In vivo and in vitro antiarrhythmic effects of SSR149744C in animal models of atrial fibrillation and ventricular arrhythmias.  J Cardiovasc Pharmacol. 2005;  45 125-135
• 8 Gautier P, Guillemare E, Marion A. et al . Electrophysiologic characterization of dronedarone in guinea pig ventricular cells.  J Cardiovasc Pharmacol. 2003;  41 191-202
• 9 Djandjighian L, Planchenault J, Finance O. et al . Hemodynamic and antiadrenergic effects of dronedarone and amiodarone in animals with a healed myocardial infarction.  J Cardiovasc Pharmacol. 2000;  36 376-383
• 10 Lalevée N, Nargeot J, Barrére-Lemaire S. et al . Effects of amiodarone and dronedarone on voltage-dependent sodium current in human cardiomyocytes.  J Cardiovasc Electrophysiol. 2003;  14 885-890
• 11 Touboul P, Brugada J, Capucci A. et al . Dronedarone for prevention of atrial fibrillation: a dose-ranging study.  Eur Heart J. 2003;  24 1481-1487
• 12 Singh B N, Connolly S J, Crijns H J. et al . EURIDIS and ADONIS Investigators. N Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter.  Engl J Med. 2007;  357 987-999
• 13 Hohnloser S H, Crijns H J, van Eickels M. et al . ATHENA Investigators. Effect of dronedarone on cardiovascular events in atrial fibrillation.  N Engl J Med. 2009;  360 668-678
• 14 Davy J M, Herold M, Hoglund C. et al . ERATO Study Investigators. Dronedarone for the control of ventricular rate in permanent atrial fibrillation: the Efficacy and safety of dronedarone for the control of ventricular rate during atrial fibrillation (ERATO) study.  Am Heart J. 2008;  156 527-0
• 15 Kober L, Torp-Pedersen C, McMurray J J. et al . Dronedarone Study Group. Increased mortality after dronedarone therapy for severe heart failure.  N Engl J Med. 2008;  358 2678-2687
• 16 Tschuppert Y, Buclin T, Rothuizen L E. et al . Effect of dronedarone on renal function in healthy subjects.  Br J Clin Pharmacol. 2007;  64 785-791
• 17 Savelieva I, Camm J. Anti-arrhythmic drug therapy for atrial fibrillation: current anti-arrhythmic drugs, investigational agents, and innovative approaches.  Europace. 2008;  10 647-665
• 18 Kowey P R, Aliot E M, Capucci A. et al . Placebo-controlled double-blind dose ranging study of the efficacy and safety of SSR149744C in patients with recentatrial fibrillation/flutter.  Heart Rhythm. 2007;  4 72 (abstract)
• 19 Arya A, Silberbauer J, Sulke N, Camm A J. A phase 2 pilot study of the efficacy of AT-2042 in subjects with paroxysmal atrial fibrillation and implanted pacemakers.  Heart Rhythm. 2006;  3 164