Möglichkeiten und Grenzen der derzeitigen medikamentösen Behandlung von Vorhofflimmern

Zusammenfassung

In den vergangenen Jahrzehnten bestand die Therapie des Vorhofflimmerns (VHF) im Wesentlichen in der medikamentösen Behandlung mit den Zielen der Rhythmuskontrolle oder Frequenzkontrolle. In Zukunft werden diese Strategien durch einige weitere Ansätze ergänzt werden. Große Bedeutung wird hierbei der Verzögerung oder Verhinderung der Bildung eines strukturellen Substrates für VHF (z. B. durch ACE-Hemmer oder AT1-Antagonisten) zukommen. Auch lässt sich von einer „individualisierten” Therapie, die individuelle Charakteristika des Patienten wie das Vorliegen eines bestimmten Substrates für VHF oder genetische Prädispositionen berücksichtigt, eine höhere Erfolgsquote bei der Rhythmuskontrolle erwarten. Eine prognostische Überlegenheit der Rhythmuskontrolle unter Verwendung der bislang verfügbaren klassischen Antiarrhythmika wie Flecainid, Sotalol oder Amiodaron konnte im Vergleich zur reinen frequenzkontrollierenden Therapie nicht nachgewiesen werden. Die ATHENA-Studie war die erste Studie, in der bei VHF die Morbidität und Mortalität nach der Einnahme von Dronedaron als Antiarrhythmikum untersucht wurden.

Abstract

Treatment strategies for atrial fibrillation (AF) encompass restoration and maintenance of sinus rhythm (rhythm control) or rate control. Antiarrhythmic drugs (AADs) currently recognized for this purpose are partially efficacious in maintaining sinus rhythm but are considered to have substantial cardiac or extra-cardiac toxicity. Yet so far, no endpoint trial has shown reduced morbidity or mortality using these agents. However, the ATHENA study was the first AF study conducted where morbidity and mortality were addressed investigating dronedarone as a new ADD therapy. This review summarizes the current pharmacological approaches to AF and briefly reviews the effects of new antiarrhythmic drugs for AF.

Schlüsselwörter

Antiarrhythmika - Pathophysiologie - Pharmakologie - Therapie - Vorhofflimmern

Keywords

antiarrhythmic drugs - atrial fibrillation - pharmacology - pathophysiology - therapy

Literatur

• 1 Alboni P, Botto G L, Baldi N. et al . Outpatient treatment of recent-onset atrial fibrillation with the „pill-in-the-pocket” approach.  N Engl J Med. 2004;  351 2384-2391
• 2 Benjamin E J, Dagostino R B, Belanger A J. et al . Left atrial size and the risk of stroke and death. The Framingham Heart Study.  Circulation. 1995;  92 835-841
• 3 Davy J M, Herold M, Hoglund C. et al . 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 e1-9
• 4 Dobrev D, Ravens U. Remodeling of cardiomyocyte ion channels in human atrial fibrillation.  Basic Res Cardiol. 2003;  98 137-148
• 5 Ehrlich J R, Hohnloser S H, Nattel S. Role of angiotensin system and effects of its inhibition in atrial fibrillation: clinical and experimental evidence.  Eur Heart J. 2006;  27 512-518
• 6 Fuster V, Ryden L E, Cannom D S. et al . ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.  Circulation. 2006;  114 e257-354
• 7 Disertori M, Latini R. et al, GISSI-AF Investigators . Valsartan for prevention of recurrent atrial fibrillation.  N Engl J Med. 2009;  360 1606-1617
• 8 Goette A, Bukowska A, Lendeckel U. et al . Angiotensin II receptor blockade reduces tachycardia-induced atrial adhesion molecule expression.  Circulation. 2008;  117 732-742
• 9 Goette A, Staack T, Arndt M. et al . Increased expression of extracellular-signal regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation.  J Am Coll Cardiol. 2000;  35 1669-1677
• 10 Goette A, Lendeckel U. Non-channel drug targets in atrial fibrillation.  Pharmacol Therap. 2004;  102 17-36
• 11 Gramley F, Himmrich E, Mollnau H. et al . Recent advances in the pharmacological treatment of cardiac arrythmias.  Drugs Today (Barc). 2009;  45 807-824
• 12 Hammwöhner M, Smid J, Lendeckel U, Goette A. New drugs for atrial fibrillation.  J Interv Card Electrophysiol. 2008;  23 15-21
• 13 Healey J S, Baranchuk A, Crystal E. et al . Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis.  J Am Coll Cardiol. 2005;  45 1832-1839
• 14 Lewalter T, Lüderitz B. Arzneimitteltherapie der Herzrhythmusstörungen.  Internist. 2000;  41 S22-S33
• 15 Kannel W B, Abbott R D, Savage D D, McNamara P M. Epidemiologic features of chronic atrial fibrillation: the Framingham study.  N Engl J Med. 1982;  306 1018-1022
• 16 Krahn A D, Manfreda J, Tate R B. et al . The natural history of atrial fibrillation: incidence, risk factors and prognosis in the Manitoba follow-up study.  Am J Med. 1995;  98 476-484
• 17 Kühlkamp V, Schirdewan A, Stangl K, Homberg M, Ploch M, Beck O A. Use of metoprolol cr/xl to maintain sinus rhythm after conversion from persistent atrial fibrillation.  J Am Coll Cardiol. 2000;  36 139-146
• 18 Lafuente-Lafuente C, Mouly S, Longas-Tejero M A, Bergmann J F. Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation.  Cochrane Database Syst Rev. 2007;  CD005049
• 19 Lafuente-Lafuente C, Mouly S, Longas-Tejero M A. et al . Antiarrhythmic drugs for maintaining sinus rhythm after cardioversion of atrial fibrillation: a systematic review of randomized controlled trials.  Arch Intern Med. 2006;  166 719-728
• 20 Lee S H, Chen S A, Chiang C E. et al . Comparisons of oral propafenone and quinidine as an initial treatment option in patients with symptomatic paroxysmal atrial fibrillation: a double-blind, randomized trial.  J Intern Med. 1996;  239 253-260
• 21 Li D, Fareh S, Leung T K, Nattel S. Promotion of atrial fibrillation by heart failure in dogs: atrial remodeling of a different sort.  Circulation. 1999;  100 87-95
• 22 Lip G YH, Beevers D G. History, epidemiology and importance of atrial fibrillation.  Br Med J. 1995;  311 1361-1363
• 23 Meinertz T, Lip G Y, Lombardi F. et al . Efficacy and safety of propafenone sustained release in the prophylaxis of symptomatic paroxysmal atrial fibrillation (The European Rythmol/Rytmonorm Atrial Fibrillation Trial [ERAFT] Study).  Am J Cardiol. 2002;  90 1300-1306
• 24 Nattel S, Li D, Yue L. Basic mechanisms of atrial fibrillation – very new insights into old ideas.  Ann Rev Physiol. 2000;  62 51-77
• 25 Nattel S. New ideas about atrial fibrillation 50 years on.  Nature. 2002;  415 219-226
• 26 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
• 27 Singh B N, Connolly S J, Crijns H J. et al . Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter.  N Engl J Med. 2007;  357 987-999
• 28 Torp-Pedersen C, Moller M, Bloch-Thomsen P E. et al . Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group.  N Engl J Med. 1999;  341 857-865
• 29 Wyse D G, Waldo A L, DiMarco J P. et al . A comparison of rate control and rhythm control in patients with atrial fibrillation.  N Engl J Med. 2002;  347 1825-1833
• 30 Zellerhoff S, Goette A, Kirchhof P. Antikoagulation bei Vorhofflimmern.  Herzschrittmacherther Elektrophysiol. 2006;  17 89-94
• 31 Ahmed S, Rienstra M, Crijns H J. et al . Continous vs episodic prophylactic treatment with amiodarone for the prevention of atrial fibrillation: a randomized trial.  JAMA. 2008;  300 1784-1792
• 32 Hohnloser S H, Crijns H JGM, van Eickels M. et al . Effect of dronedarone on cardiovascular events in atrial fibrillation.  N Engl J Med. 2009;  360 668-678