Thrombembolieprophylaxe bei Patienten mit Vorhofflimmern

Zusammenfassung

In der vorliegenden Übersichtsarbeit wird die aktuelle Datenlage zur Thrombembolieprophylaxe und insbesondere zur Prophylaxe des ischämischen Schlaganfalles bei Patienten mit Vorhofflimmern zusammengefasst und bewertet. Die Indikation zur Thrombembolieprophylaxe basiert auf der individuellen Risikobewertung z. B. mittels CHA₂DS₂-VASc- und HAS-BLED-Score. Bei Indikation zur oralen Antikoagulation stellen VitaminK-Antagonisten die Standardtherapie dar. Sie verhindern etwa zwei Drittel der erwarteten ischämischen Schlaganfälle, führen jedoch jährlich bei ca. 1% der Patienten zu schweren Blutungen. Als Alternative etablieren sich zunehmend die neuen oral applizierbaren direkten Thrombin- und Faktor-XaAntagonisten (z. B. Dabigatran, Rivaroxaban, Apixaban, Edoxaban). Der monokausale Wirkmechanismus führt zu einer im Vergleich zu VitaminK-Antagonisten besseren Steuerbarkeit mit günstigerem Nutzen-Risikoprofil (RELY-Studie, Rocket-AF-Studie, ARISTOTLE-Studie). So war in der ARISTOTLE-Studie unter Apixaban der kombinierte Endpunkt (ischämische Schlaganfälle, hämorrhagische Schlaganfälle, periphere Embolien) um 21%, die Rate an schweren Blutungen um 31% und die Rate an hämorrhagischen Schlaganfällen um annähernd 50% im Vergleich zu Warfarin reduziert. Bei Patienten, denen aufgrund eines hohen Blutungsrisikos keine orale Antikoagulation angeboten werden kann, sollte der transvenöse Verschluss des Vorhofohres mittels Okkludersystem diskutiert werden. ASS und andere Thrombozytenaggregationshemmer haben bei Vorhofflimmern keine gesicherte thrombembolieprophylaktische Wirkung und werden nicht mehr empfohlen.

Summary

In this review article, the current recommendations for prevention of thromboembolic complications in patients with atrial fibrillation are summarized and discussed. Preventive strategies of thromboembolic complications depend on the individual risk of the patient, e. g. stratified with the CHA₂DS₂-VASc score and the HAS-BLED score. If oral anticoagulation is adequate, vitamin K antagonists are the backbone of therapy. Vitamin K antagonists result in a relative risk reduction of 65 to 70% for ischemic strokes. However, the annual risk for major bleeding events exceeds 1% in most studies. In this context, novel oral direct thrombin or factor Xa antagonists (e. g. dabigatran, rivaroxaban, apixaban, edoxaban) are highly anticipated since the risk/benefit ratio presumably is superior to that of vitamin K antagonists. Recent data support this (RELY trial, Rocket-AF trial, ARISTOTLE trial). In the ARISTOTLE trial, apixaban compared to warfarin resulted in a relative risk reduction of 21% for the composite endpoint (ischemic strokes, hemorrhagic strokes, systemic embolic events), a relative risk reduction of 31% for major bleeding events, and a relative risk reduction of almost 50% for hemorrhagic strokes. In patients not eligible for oral anticoagulation due to an excessive bleeding risk, transvenous left atrial appendage occlusion is an alternative treatment option. ASS has no proven effect in patients with atrial fibrillation and is not recommended anymore.

Schlüsselwörter

Vorhofflimmern, Thrombembolieprophylaxe - Marcumar - Dabigatran - Apixaban - Vorhofohrverschluss

Keywords

Atrial fibrillation - stroke - warfarin - dabigatran - apixaban - watchman device

• Literatur

• 1 Go AS. et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001; 285: 2370-5.
• 2 Kirchhof P. et al. Outcome parameter for trials in atrial fibrillation: executive summary. Recommendations from a consensus conference organized by the German Atrial Fibrillation Competence NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eur Heart J 2007; 28: 2803-17.
• 3 Lip GY. et al. Refining clinical risk stratification for prediction of stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on atrial fibrillation. Chest 2010; 137: 263-72.
• 4 Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patient who have nonvalvular atrial fibrillation. Ann Intern Med 2007; 146: 857-67.
• 5 Camm AJ. et al. for the Task Force for the management of atrial fibrillation of the European Society of Cardiology: Guidelines for the management of atrial fibrillation. Eur Heart J 2010; 31: 2369-429.
• 6 Sato H. et al. Low-dose aspirin for prevention of stroke in low-risk patients with atrial fibrillation: Japan Atrial Fibrillation Stroke Trial. Stroke 2006; 37: 447-51.
• 7 Mant J. et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA). Lancet 2007; 370: 493-503.
• 8 Connolly SJ. et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events (ACTIVE W). Lancet 2006; 367: 190-12.
• 9 Connolly SJ. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-51.
• 10 Eikelboom JW. et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation. Circulation 2011; 123: 2363-72.
• 11 Stangier J. et al. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin Pharmacokinet 2010; 49: 259-68.
• 12 Patel MR. et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011 10. August; E-Pub ahead of print.
• 13 Connolly S. et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011; 364: 806-17.
• 14 Granger CB. et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011 28. August; E-Pub ahead of print.
• 15 ACCF/AHA Task Force Members. 2011 ACCF/ AHA/HRS Focused update on the management of patients with atrial fibrillation (update on dabigatran). Heart Rhythm 2011; 8: 1-8.
• 16 Pisters R. et al. A novel userfriendly score (HAS-BLED) to assess one-year risk of major bleeding in atrial fibrillation patients: The Euro Heart Survey. Chest. 2010 March 18, Epub ahead of print.
• 17 Holmes DR. et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation. Lancet 2009; 374: 534-42.