Subscribe to RSS
DOI: 10.1055/s-0041-102000
Vorhofflimmern: Wie effektiv und sicher sind die direkten oralen Antikoagulanzien zur Prävention von Schlaganfällen?
Stroke prevention with direct oral anticoagulants in patients with non-valvular atrial fibrillationPublication History
Publication Date:
13 May 2015 (online)

Zusammenfassung
Die Entwicklung der direkten oralen Antikoagulantien stellt einen der größten medizinischen Fortschritte der letzten 10 Jahre dar. Im Vergleich zu den Vitamin K Antagonisten sind diese Medikamente (Dabigatran als Thrombin-Inhibitor, Rivaroxaban, Apixaban und Edoxaban als Faktor Xa Hemmer) aufgrund ihrer pharmakologischen Eigenschaften ungleich einfacher anzuwenden. Alle direkten oralen Antikoagulantien weisen eine bessere Wirksamkeit und eine höhere Sicherheit als die Vitamin K Antagonisten auf, wie in den entsprechenden Zulassungsstudien an mehr als 71 000 Patienten gezeigt worden ist. Insbesondere die viel geringere Häufigkeit intrakranieller Blutungen machen die DOACs zu Medikamenten der ersten Wahl für die primäre und sekundäre Schlaganfallprävention bei nicht-valvulärem Vorhofflimmern.
Abstract
The development of the direct oral anticoagulants (DOACs) represents one of the major breakthroughs in modern medicine over the last decade. Compared to vitamin K antagonists, all DOACs (dabigatran as a thrombin-Inhibitor, rivaroxaban, apixaban and edoxaban as factor Xa inhibitors) are much easier to handle due to their pharmacological properties. All DOACS are more efficacious and safer as vitamin K antagonists as demonstrated in the pivotal studies in more than 71 000 patients. Particularly the much lower risk of intracerebral bleeding complications is the reason why the DOACs should be preferred over vitamin K antagonists in patients with non-valvular atrial fibrillation.
-
Literatur
- 1 Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: The Framingham Study. Stroke 1991; 22: 983-988
- 2 Hohnloser SH, Pajitnev D, Pogue J et al. Incidence of stroke in paroxysmal versus sustained atrial fibrillation in patients taking oral anticoagulation or combined antiplatelet therapy: an ACTIVE W Substudy. J Am Coll Cardiol 2007; 50: 2156-161
- 3 Marini C, De Santis F, Sacco S et al. Contribution of atrial fibrillation to incidence and outcome of ischemic stroke: results from a population-based study. Stroke 2005; 36: 1115-1119
- 4 Dulli DA, Stanko H, Levine RL. Atrial fibrillation is associated with severe acute ischemic stroke. Neuroepidemiology 2003; 22: 118-123
- 5 Lamassa M, Di Carlo A, Pracucci G et al. Characteristics, outcome, and care of stroke associated with atrial fibrillation in Europe. Stroke 2001; 32: 392-398
- 6 Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology 2007; 69: 546-554
- 7 Hart R, Benavente O, McBride R, Pearce L. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med 1999; 131: 492-501
- 8 Mant J, Hobbs FDR, Fletcher K 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
- 9 Camm AJ, Lip GYH, De Caterina R et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation. Europ Heart J 2012; 33: 2719-2749
- 10 Ansell J, Hirsh J, Hylek E et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (Suppl. 06) 160S-198S
- 11 Turpie AG. New oral anticoagulants in atrial fibrillation. Eur Heart J 2008; 29: 155-165
- 12 Hylek E, Singer D. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 1994; 120: 897-902
- 13 Oden A, Fahlen M, Hart RG. Optimal INR for prevention of stroke and death in atrial fibrillation: a critical appraisal. Thromb Res 2006; 117: 493-499
- 14 Glader EL, Sjolander M, Eriksson M, Lundberg M. Persistent use of secondary preventive drugs declines rapidly during the first 2 years after stroke. Stroke 2010; 41: 397-401
- 15 Ogilvie IM, Newton N, Welner SA et al. Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am J Med 2010; 123: 638-645
- 16 Kakkar AK, Mueller I, Bassandet JP et al. Risk profiles and antithrombotic treatment of patients newly diagnosed with atrial fibrillation at risk of stroke: Perspectives from the International, Observational, Prospective GARFIELD Registry. PLoS One 2013; 8: e63479
- 17 Meinertz T, Kirch W, Rosin L et al. Management of atrial fibrillation by primary care physicians in Germany: baseline results of the ATRIUM registry. Clin Res Cardiol 2011; 100: 897-905
- 18 Baker JWL, Cios DA, Sander SD, Coleman CI. Meta-Analysis to assess the quality of warfarin control in atrial fibrillation patients in the United States. J Manag Care Pharm 2009; 15: 2344-2252
- 19 Dlott JS, George RA, Huang X et al. National assessment of warfarin anticoagulation therapy for stroke prevention in atrial fibrillation. Circulation 2014; 129: 1407-1414
- 20 Connolly SJ, Ezekowitz MD, Yusuf S et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-1151
- 21 Granger C, Alexander J, McMurray J et al. Apixaban versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2011; 365: 981-992
- 22 Patel MR, Mahaffey KW, Garg J et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883-891
- 23 Giugliano RP, Ruff CT, Braunwald E et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369: 2093-2104
- 24 Ruff TR, Giugliano RP, Braunwald E et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014; 383: 955-962
- 25 Hylek E, D’Antonio J, Evans-Molina C et al. Translating the results of randomized trials into clinical practice. Stroke 2006; 37: 1075-1080
- 26 Lip GYH, Andreotti F, Fauchier L et al. Bleeding risk assessment and management in atrial fibrillation patients. Thromb Haemost 2011; 106: 997-911
- 27 Diener HC, Connolly SJ, Ezekowitz MD et al. Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial. Lancet Neurol 2010; 9: 1157-1163
- 28 Hankey GH, Patel MR, Stevens SR et al. Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF. Lancet Neurol 2012; 11: 315-322
- 29 Easton JD, Lopes RD, Bahit MC et al. Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial. Lancet Neurol 2012; 11: 503-511
- 30 Hohnloser SH, Oldgren J, Yang S et al. Myocardial ischemic events in patients with atrial fibrillation treated with dabigatran or warfarin in the RE-LY (Randomized evaluation of long-term anticoagulation therapy) trial. Circulation 2012; 125: 669-676
- 31 Dans AL, Connolly SJ, Wallentin L et al. Concomitant Use of Antiplatelet Therapy with Dabigatran or Warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY®) Trial. Circulation 2013; 127: 634-640
- 32 Bahit MC, Lopes RD, Wojdyla DM et al. Apixaban in patients with atrial fibrillation and prior coronary artery disease: Insights from the ARISTOTLE trial. Int J Cardiol 2013; 170: 215-220
- 33 Cappato R, Ezekowitz MD, Klein AL et al. Rivaroxaban versus Vitamin K Antagonists for Cardioversion in Atrial Fibrillation. Eur Heart J 2014; 35: 3346-3355
- 34 Nagarakanti R, Ezekowitz MD, Oldgren J et al. Dabigatran versus warfarin in patients with atrial fibrillation. An analysis of patients undergoing cardioversion. Circulation 2011; 123: 131-136
- 35 Flaker G, Lopes RD, Al-Khatib SM et al. Efficacy and safety of apixaban in patients after cardioversion for atrial fibrillation. Insights from the ARISTOTLE trial. J Am Coll Cardiol 2014; 63: 1082-1087
- 36 Xian Y, Liang L, Smith EE et al. Risks of intracranial hemorrhage among patients with acute ischemic stroke receiving warfarin and treated with intravenous tissue plasminogen activator. JAMA 2012; 307: 2600-2608
- 37 Diener HC, Foerch C, Riess H et al. Treatment of acute ischaemic stroke with thrombolysis or thrombectomy in patients receiving anti-thrombotic treatment. Lancet Neurol 2013; 12: 677-688
- 38 Heidbuchel H, Verhamme P, Alings M et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013; 15: 625-651
- 39 Hylek EM, Held C, Alexander JH et al. Major Bleeding in Patients with Atrial Fibrillation Receiving Apixaban or Warfarin in the ARISTOTLE Trial: Predictors, Characteristics, and Clinical Outcomes. J Am Coll Cardiol 2014; 63: 2141-2147
- 40 Schiele F, van Ryn J, Canada K et al. A specific antidote for dabigatran: functional and structural Characterization. Blood 2013; 121: 3554-3562