Prävention des Schlaganfalls durch Behandlung des Vorhofflimmerns

Zusammenfassung

Vorhofflimmern (VHF) ist die häufigste Herzrhythmusstörung und nimmt mit dem Alter zu. Sie tritt bei etwa 1 % der Erwachsenen und 9 % der über 80-Jährigen auf. Die Prognose für das Jahr 2050 sagt eine Verdreifachung der Prävalenz voraus. VHF ist mit einer erhöhten kardiovaskulären Morbidität und Mortalität vergesellschaftet und Patienten mit VHF weisen ein 5-fach erhöhtes Schlaganfallrisiko auf. Etwa jeder 4. ischämische Schlaganfall ist Folge einer kardialen Embolie. Die Schlaganfälle bei Patienten mit VHF sind in der Regel schwerer und öfter tödlich im Vergleich zu Patienten ohne VHF. Therapiestrategien zur Senkung der kardiovaskulären Morbidität und Mortalität und der Schlaganfallrate sind die Antikoagulation mit Vitamin-K-Antagonisten und die Frequenz- oder Rhythmuskontrolle. Nun stehen für beide Therapiestrategien neue Wirkstoffe zur Verfügung. Für Dronedaron, ein neues Amiodaron-ähnliches Antiarrhythmikum, ergibt eine post-hoc-Analyse Hinweise auf eine Reduktion des Schlaganfallrisikos um 34 % (p = 0,027) bei Patienten mit nicht-permanentem VHF. Dabigatran, ein direkter oraler Thrombininhibitor, war in der RE-LY-Studie im Vergleich zu Warfarin wirksamer in der Prävention embolischer Ereignisse und sicherer. Weitere Studien werden zeigen, bei welchen Patienten diese beiden neuen Medikamente die Prävention kardiovaskulärer Morbidität und Mortalität sowie des Schlaganfalls verbessern können.

Abstract

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting about 1 % of adults; its prevalence increases with age. Nine percent of those aged 80 years and older have AF. AF is associated with increased cardiovascular mortality and morbidity, and the risk of stroke ist increased by the factor 5.

Stroke in patients with AF is more severe and more likely to be fatal. Prevention of thromboembolism with oral anticoagulants and rate- or rhythm-control are the main therapeutic strategies for patients with AF. But vitamin K antagonists, which reduce the risk of stroke in patients with AF, are underutilized. Until recently, rhythm-control studies did not show any benefit in the prevention of cardiovascular complications, including stroke. New drugs have recently become available that may add to the therapeutic options. A post-hoc analysis of dronedarone, a novel antiarrhythmic drug, suggests a reduction of the risk of stroke by 34 % (p =  0.027) in patients with non-permanent atrial fibrillation in addition to standard therapy, including antithrombotics. The novel anticoagulant dabigatran showed stroke reductions and improved safety in the RE-LY trial which compared its efficacy with warfarin.

On-going studies will help to identify those patients with AF who are likely to benefit from these novel antithrombotic and antiarrhythmic agents by reducing the risk of stroke.

Schlüsselwörter

Vorhofflimmern - Schlaganfall - Antiarrhythmika - Thrombininhibitor - Antikoagulation

Keywords

atrial fibrillation - ischemic stroke - antiarrhythmic drug - thrombin inhibitor - anticoagulation

Literatur

• 1 Baetz B E, Spinler S A. Dabigatran etexilate: an oral direct thrombin inhibitor for prophylaxis and treatment of thromboembolic diseases.  Pharmacotherapy. 2008;  28 1354-1373
• 2 Botto G L, Padeletti L, Santini M, Capucci A, Gulizia M, Zolezzi F. et al . Presence and duration of atrial fibrillation detected by continuous monitoring: crucial implications for the risk of thromboembolic events.  J Cardiovasc Electrophysiol. 2009;  20 241-248
• 3 Brignole M, Vardas P, Hoffman E, Huikuri H, Moya A, Ricci R. et al . Indications for the use of diagnostic implantable and external ECG loop recorders.  Europace. 2009;  11 671-687
• 4 Capucci A, Santini M, Padeletti L, Gulizia M, Botto G, Boriani G. et al . Monitored atrial fibrillation duration predicts arterial embolic events in patients suffering from bradycardia and atrial fibrillation implanted with antitachycardia pacemakers.  J Am Coll Cardiol. 2005;  46 1913-1920
• 5 Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, Chrolavicius S. 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): a randomised controlled trial.  Lancet. 2006;  367 1903-1912
• 6 Connolly S J, Crijns H J, Torp-Pedersen C, van Eickels M, Gaudin C, Page R L. et al . Analysis of stroke in ATHENA: a placebo-controlled, double-blind, parallel-arm trial to assess the efficacy of dronedarone 400 mg BID for the prevention of cardiovascular hospitalization or death from any cause in patients with atrial fibrillation/atrial flutter.  Circulation. 2009;  120 1174-1180
• 7 Connolly S J, Ezekowitz M D, Yusuf S, Eikelboom J, Oldgren J, Parekh A. et al . Dabigatran versus warfarin in patients with atrial fibrillation.  N Engl J Med. 2009;  361 1139-1151
• 8 Connolly S J, Pogue J, Hart R G, Hohnloser S H, Pfeffer M, Chrolavicius S. et al . Effect of clopidogrel added to aspirin in patients with atrial fibrillation.  N Engl J Med. 2009;  360 2066-2078
• 9 Fetsch T, Bauer P, Engberding R, Koch H P, Lukl J, Meinertz T. et al . Prevention of atrial fibrillation after cardioversion: results of the PAFAC trial.  Eur Heart J. 2004;  25 1385-1394
• 10 Fuster V, Ryden L E, Cannom D S, Crijns H J, Curtis A B, Ellenbogen K A. 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
• 11 Go A S, Hylek E M, Phillips K A, Chang Y, Henault L E, Selby J V. 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 2370-2375
• 12 Goto S, Bhatt D L, Rother J, Alberts M, Hill M D, Ikeda Y. et al . Prevalence, clinical profile, and cardiovascular outcomes of atrial fibrillation patients with atherothrombosis.  Am Heart J. 2008;  156 855-63, 863 e2
• 13 Grau A J, Weimar C, Buggle F, Heinrich A, Goertler M, Neumaier S. et al . Risk factors, outcome, and treatment in subtypes of ischemic stroke: the German stroke data bank.  Stroke. 2001;  32 2559-2566
• 14 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
• 15 Hohnloser S H, Crijns H J, van Eickels M, Gaudin C, Page R L, Torp-Pedersen C. et al . Effect of dronedarone on cardiovascular events in atrial fibrillation.  N Engl J Med. 2009;  360 668-678
• 16 Hylek E M, Go A S, Chang Y, Jensvold N G, Henault L E, Selby J V. et al . Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation.  N Engl J Med. 2003;  349 1019-1026
• 17 Jabaudon D, Sztajzel J, Sievert K, Landis T, Sztajzel R. Usefulness of ambulatory 7-day ECG monitoring for the detection of atrial fibrillation and flutter after acute stroke and transient ischemic attack.  Stroke. 2004;  35 1647-1651
• 18 Kirchhof P, Auricchio A, Bax J, Crijns H, Camm J, Diener H C. et al . Outcome parameters for trials in atrial fibrillation: executive summary.  Eur Heart J. 2007;  28 2803-2817
• 19 Lavy S, Stern S, Melamed E, Cooper G, Keren A, Levy P. Effect of chronic atrial fibrillation on regional cerebral blood flow.  Stroke. 1980;  11 35-38
• 20 Lin H J, Wolf P A, Kelly-Hayes M, Beiser A S, Kase C S, Benjamin E J. et al . Stroke severity in atrial fibrillation. The Framingham Study.  Stroke. 1996;  27 1760-1764
• 21 Mant J, Hobbs F D, Fletcher K, Roalfe A, Fitzmaurice D, Lip G Y. 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): a randomised controlled trial.  Lancet. 2007;  370 493-503
• 22 Marini C, De Santis F, Sacco S, Russo T, Olivieri L, Totaro R. et al . Contribution of atrial fibrillation to incidence and outcome of ischemic stroke: results from a population-based study.  Stroke. 2005;  36 1115-1119
• 23 Nieuwlaat R, Dinh T, Olsson S B, Camm A J, Capucci A, Tieleman R G. et al . Should we abandon the common practice of withholding oral anticoagulation in paroxysmal atrial fibrillation?.  Eur Heart J. 2008;  29 915-922
• 24 Page R L, Wilkinson W E, Clair W K, McCarthy E A, Pritchett E L. Asymptomatic arrhythmias in patients with symptomatic paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia.  Circulation. 1994;  89 224-227
• 25 Patel C, Yan G -X, Kowey P R. Dronedarone.  Circulation. 2009;  120 636-644
• 26 Sherman D G. Stroke prevention in atrial fibrillation: pharmacological rate versus rhythm control.  Stroke. 2007;  38 615-617
• 27 Tagawa M, Takeuchi S, Chinushi M, Saeki M, Taniguchi Y, Nakamura Y. et al . Evaluating patients with acute ischemic stroke with special reference to newly developed atrial fibrillation in cerebral embolism.  Pacing Clin Electrophysiol. 2007;  30 1121-1128
• 28 Wolf P A, Abbott R D, Kannel W B. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study.  Stroke. 1991;  22 983-988
• 29 Wyse D G, Waldo A L, DiMarco J P, Domanski M J, Rosenberg Y, Schron E B. et al . A comparison of rate control and rhythm control in patients with atrial fibrillation.  N Engl J Med. 2002;  347 1825-1833