Neue Antikoagulanzien für die Thromboembolieprophylaxe bei Vorhofflimmern

 

 Buy Article Permissions and Reprints

Zusammenfassung

Vorhofflimmern ist die häufigste Herzrhythmusstörung und Hauptursache für kardioembolische Schlaganfälle. Die Thromboembolieprophylaxe erfolgt in Abhängigkeit des individuellen Risikos mit Acetylsalicylsäure (ASS) oder Vitamin-K-Antagonisten. Die Effektivität und Sicherheit der oralen Antikoagulation wird durch eine enge therapeutische Breite und inter- und intraindividuellen Schwankungen des INR-Wertes aufgrund genetischer Dispositionen sowie alimentärer Einflüsse, Dosierungsfehler, zu seltene INR-Kontrolle und Arzneimittelinteraktionen beträchtlich limitiert. Neue, oral verfügbare Substanzen mit unterschiedlichen Wirkmechanismen stellen vielversprechende Therapiealternativen dar. In dieser Arbeit werden die Faktor-Xa-Inhibitoren Apixaban, Rivaroxaban, der direkte Thrombininhibitor Dabigatranetexilat mit ihren korrespondierenden Phase-III-Studien (ARISTOTLE, ROCKET-AF, RE-LY) bei Patienten mit Vorhofflimmern näher erläutert und das Studiendesign und – soweit verfügbar – auch die Studienergebnisse verglichen.

Abstract

The most frequent cardiac arrhythmia and main cause for cardio-embolic stroke is atrial fibrillation. Prophylaxis for thrombembolic events is performed regarding individual risk of patients with either ASS or vitamin-K-antagonists. Efficacy and safety of oral anticoagulation is limited by a narrow therapeutical range as well as by inter- and intraindividual variability of INR-values due to genetic disposition, differences in alimentation, dosage errors, rare control of INR-levels and drug-interactions. New oral anticoagulants with different mechanisms of action may be a promising therapeutic option in future. This review addresses the new anticoagulants Apixaban, Rivaroxban and Dabigatranetexilat with the design and as available the results of the corresponding phase-III-trials in atrial fibrillation (ARISTOTLE, ROCKET-AF, RE-LY).

Literatur

• 1 Ansell J, Hollowell J, Pengo V. et al . Descriptive analysis of the process and quality of oral anticoagulation management in real-life practice in patients with chronic non-valvular atrial fibrillation: the international study of anticoagulation management (ISAM).  J Thromb Thrombolysis. 2007;  23 83-91
  Google Scholar
• 2 Connolly S J, Ezekowitz M D, Yusuf S. et al . Dabigatran versus warfarin in patients with atrial fibrillation.  New Engl J Med. 2009;  361 1139-1151
  Google Scholar
• 3 Diener H C. Stroke prevention using the oral direct thrombin inhibitor ximelagatran in patients with non-valvular atrial fibrillation. Pooled analysis from the SPORTIF III and V studies.  Cerebrovasc Dis. 2006;  21 279-293
  Google Scholar
• 4 Eikelboom J W, O’Donnell M, Yusuf S. et al . Rationale and design of AVERROES: apixaban versus acetylsalicylic acid to prevent stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment.  Am Heart J. 2010;  159 348-353 e341
  Google Scholar
• 5 Fetsch T, Bauer P, Engberding R. et al . Prevention of atrial fibrillation after cardioversion: results of the PAFAC trial.  European heart journal. 2004;  25 1385-1394
  Google Scholar
• 6 Fuster V, Ryden L E, Cannom D S. et al . ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation – excutive summary.  Rev Port Cardiol. 2007;  26 383-446
  Google Scholar
• 7 Goto S, Bhatt D L, Rother J. et al . Prevalence, clinical profile, and cardiovascular outcomes of atrial fibrillation patients with atherothrombosis.  Am Heart J. 2008;  156 855-863, 863 e852
  Google Scholar
• 8 Grau A J, Weimar C, Buggle F. et al . Risk factors, outcome, and treatment in subtypes of ischemic stroke: the German stroke data bank.  Stroke. 2001;  32 2559-2566
  Google Scholar
• 9 Group SRiAFW . Independent predictors of stroke in patients with atrial fibrillation: a systematic review.  Neurology. 2007;  69 546-554
  Google Scholar
• 10 Hankey G J, Eikelboom J W. Antithrombotic drugs for patients with ischaemic stroke and transient ischaemic attack to prevent recurrent major vascular events.  Lancet Neurol. 2010;  9 273-284
  Google Scholar
• 11 Hart R G, Pearce L A, Aguilar M I. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation.  Ann Intern Med. 2007;  146 857-867
  Google Scholar
• 12 Hylek E M, Evans-Molina C, Shea C, Henault L E, Regan S. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation.  Circulation. 2007;  115 2689-2696
  Google Scholar
• 13 Kirchhof P, Bax J, Blomstrom-Lundquist C. et al . Early and comprehensive management of atrial fibrillation: executive summary of the proceedings from the 2nd AFNET-EHRA consensus conference ‘research perspectives in AF’.  Eur Heart J. 2009;  30 2969-2977c
  Google Scholar
• 14 Kubitza D, Becka M, Roth A, Mueck W. Dose-escalation study of the pharmacokinetics and pharmacodynamics of rivaroxaban in healthy elderly subjects.  Curr Med Res Opin. 2008;  24 2757-2765
  Google Scholar
• 15 Kubitza D, Becka M, Voith B, Zuehlsdorf M, Wensing G. Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59 – 7939, an oral, direct factor Xa inhibitor.  Clin Pharmacol Ther. 2005;  78 412-421
  Google Scholar
• 16 Lin H J, Wolf P A, Kelly-Hayes M. et al . Stroke severity in atrial fibrillation. The Framingham Study.  Stroke. 1996;  27 1760-1764
  Google Scholar
• 17 Lopes R D, Alexander J H, Al-Khatib S M. et al . Apixaban for reduction in stroke and other ThromboemboLic events in atrial fibrillation (ARISTOTLE) trial: design and rationale.  Am Heart J. 2010;  159 331-339
  Google Scholar
• 18 Mann K G, Brummel K, Butenas S. What is all that thrombin for?.  J Thromb Haemost. 2003;  1 1504-1514
  Google Scholar
• 19 Miyasaka Y, Barnes M E, Gersh B J. et al . Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence.  Circulation. 2006;  114 119-125
  Google Scholar
• 20 Rother J, Laufs U. Prävention des Schlaganfalls durch Behandlung des Vorhofflimmerns.  Dtsch Med Wochenschr. 2010;  135 Suppl 2 S55-58
  Google Scholar
• 21 Sherman D G. Stroke prevention in atrial fibrillation: pharmacological rate versus rhythm control.  Stroke. 2007;  38 615-617
  Google Scholar
• 22 Singer D E, Albers G W, Dalen J E. et al . Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).  Chest. 2008;  33 546S-592S
  Google Scholar
• 23 van Ryn J, Stangier J, Haertter S. et al . Dabigatran etexilate – a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity.  Thromb Haemost. 2010;  03 1116-1127
  Google Scholar
• 24 van Walraven C, Jennings A, Oake N, Fergusson D, Forster A J. Effect of study setting on anticoagulation control: a systematic review and metaregression.  Chest. 2006;  29 1155-1166
  Google Scholar
• 25 Zhang D, He K, Raghavan N. et al . Comparative metabolism of 14C-labeled apixaban in mice, rats, rabbits, dogs, and humans.  Drug Metab Dispos. 2009;  37 1738-1748
  Google Scholar

Dr. Magnus Baumhäkel

Klinik für Innere Medizin III
Universitätsklinikum des Saarlandes

66421 Homburg/Saar

Phone: 06841/1623289

Fax: 06841/1623446

Email: magnus@baumhaekel.de