Aktueller Stellenwert der Antidots unter NOAK-Therapie

Zusammenfassung

Die oralen Nicht-Vitamin-K-Antagonisten (NOAK) sind ein fester Bestandteil der Therapie des nicht-valvulären Vorhofflimmerns, der Beinvenenthrombose und der Lungenembolie. Den klar bestehenden Vorteilen steht als Nachteil das Fehlen spezifischer Antidot gegenüber. Zurzeit ist nur für Dabigatran ein spezifisches Antidot erhältlich. Idarucizumab ist nach i. v.-Gabe schnell wirksam. Für die Faktor-Xa-Antagonisten sind spezifische Antidots noch nicht verfügbar.

• Literatur

• 1 Connolly SJ, Ezekowitz MD, Yusuf S. et al.; RE-LY Steering Committee and Investigators Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-1151
• 2 Patel MR, Mahaffey KW, Garg J. et al.; ROCKET AF Steering Committee, for the ROCKET AF Investigators Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883-891
• 3 Granger CB, Alexander JH, McMurray JJ. et al.; ARISTOTLE Committees and Investigators Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365: 981-992
• 4 Giugliano RP, Ruff CT, Braunwald E. et al.; ENGAGE AF-TIMI 48 Investigators Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369: 2093-2104
• 5 Pollack Jr CV, Reilly PA, Eikelboom J. et al. Idarucizumab for dabigatran reversal. N Engl J Med 2015; 373: 511-520
• 6 Connolly SJ, Milling Jr TJ, Eikelboom JW. et al.; ANNEXA-4 Investigators Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med 2016; 375: 1131-1141
• 7 Ruff CT, 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
• 8 Hemphill 3rd JC, Greenberg SM, Anderson CS. et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2015; 46: 2032-2060
• 9 Lip GY, Lane DA. Assessing bleeding risk in atrial fibrillation with the HAS-BLED and ORBIT scores: clinical application requires focus on the reversible bleeding risk factors. Eur Heart J 2015; 36: 3265-3267
• 10 Sherwood MW, Nessel CC, Hellkamp AS. et al. Gastrointestinal bleeding in patients with atrial fibrillation treated with rivaroxaban or warfarin: ROCKET AF Trial. J Am Coll Cardiol 2015; 66: 2271-2281
• 11 Böhm M, Ezekowitz MD, Connolly SJ. et al. Changes in renal function in patients with atrial fibrillation: an analysis from the RE-LY Trial. J Am Coll Cardiol 2015; 65: 2481-2493
• 12 Fordyce CB, Hellkamp AS, Lokhnygina Y. et al.; ROCKET AF Steering Committee and Investigators On-treatment outcomes in patients with worsening renal function with rivaroxaban compared with warfarin: insights from ROCKET AF. Circulation 2016; 134: 37-47
• 13 Alikhan R, Rayment R, Keeling D. et al. The acute management of haemorrhage, surgery and overdose in patients receiving dabigatran. Emerg Med J 2014; 31: 163-168
• 14 Powers WJ, Derdeyn CP, Biller J. et al.; on behalf of the American Heart Association Stroke Council 2015 American Heart Association/American Stroke Association focused update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2015; 46: 3020-3035
• 15 Connolly SJ, Eikelboom J, Joyner C. et al.; AVERROES Steering Committee and Investigators Apixaban in patients with atrial fibrillation. N Engl J Med 2011; 364: 806-817
• 16 Heidbuchel H, Verhamme P, Alings M. et al.; European Heart Rhythm Association 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
• 17 Healey JS, Eikelboom J, Douketis J. et al.; RE-LY Investigators Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) randomized trial. Circulation 2012; 126: 343-348
• 18 Sherwood MW, Douketis JD, Patel MR. et al.; ROCKET AF Investigators Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: results from the Rivaroxaban-Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Circulation 2014; 129: 1850-1859
• 19 Garcia D, Alexander JH, Wallentin L. et al. Management and clinical outcomes in patients treated with apixaban vs warfarin undergoing procedures. Blood 2014; 124: 3692-3698
• 20 Gibson CM, Mehran R, Bode C. et al. An open-label, randomized, controlled, multicenter study exploring two treatment strategies of rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment strategy in subjects with atrial fibrillation who undergo percutaneous coronary intervention (PIONEER AF-PCI). Am Heart J 2015; 169: 472-478
• 21 Dewilde WJ, Oirbans T, Verheugt FW. et al.; WOEST Study Investigators Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 2013; 381: 1107-1115
• 22 Caldeira D, Costa J, Ferreira JJ. et al. Non-vitamin K antagonist oral anticoagulants in the cardioversion of patients with atrial fibrillation: systematic review and meta-analysis. Clin Res Cardiol 2015; 104: 582-590
• 23 Goette A, Merino JL, Ezekowitz MD. et al.; ENSURE-AF investigators Edoxaban versus enoxaparin-warfarin in patients undergoing cardioversion of atrial fibrillation (ENSURE-AF): a randomised, open-label, phase 3b trial. Lancet 2016; 388: 1995-2003
• 24 Schulman S, Carrier M, Lee AY. et al.; Periop Dabigatran Study Group Perioperative management of dabigatran: a prospective cohort study. Circulation 2015; 132: 167-173
• 25 Raval AN, Cigarroa JE, Chung MK. et al. and On behalf of the American Heart Association Clinical Pharmacology Subcommittee of the Acute Cardiac Care and General Cardiology Committee of the Council on Clinical Cardiology; Council on Cardiovascular Disease in the Young; and Council on Quality of Care and Outcomes Research Management of Patients on Non-Vitamin K Antagonist Oral Anticoagulants in the Acute Care and Periprocedural Setting: A Scientific Statement From the American Heart Association. Circulation. 2017 135. 00–00
• 26 Enriquez A, Lip GYH, Baranchuk A. Anticoagulation reversal in the era of the non-vitamin K oral anticoagulants. Europace 2016; 18: 955-964
• 27 Ruff CT, Giugliano RP, Antman EA. Management of Bleeding With Non-Vitamin K Antagonist Oral Anticoagulants in the Era of Specific Reversal Agents. Circulation 2016; 134: 248-261
• 28 Anderson CS, Heeley E, Huang Y. et al. for the INTERACT2 Investigators – Rapid Blood-Pressure Lowering in Patients with Acute Intracerebral Hemorrhage. N Engl J Med 2013; 368: 2355-2365
• 29 Beyer-Westendorf J, Förster K, Pannach S. et al. Rates, management, and outcome of rivaroxaban bleeding in daily care: results from the Dresden NOAC registry. Blood 2014; 124: 955-962
• 30 Yasaka M, Lip GY. Impact of non-vitamin k antagonist oral anticoagulants on intracranial bleeding in Asian patients with non-valvular atrial fibrillation. Circ J 2014; 78: 2367-2372
• 31 Calkins H, Willems S, Gerstenfeld EP. et al. for the RE-CIRCUIT Investigators Uninterrupted Dabigatran versus Warfarin for Ablation in Atrial Fibrillation. N Engl J Med 2017; 376: 1627-1636
• 32 Cappato R, Marchlinski FE, Hohnloser SH. et al. on behalf of the VENTURE-AF Investigators Uninterrupted rivaroxaban vs. uninterrupted vitamin K antagonists for catheter ablation in non-valvular atrial fibrillation. Eur Heart J 2015; 36: 1805-1811
• 33 Pollack CV, Reilly PA, van Ryn J. Idarucizumab for Dabigatran Reversal — Full Cohort Analysis. N Engl J Med 2017; 377: 431-441