Der Klinikarzt 2016; 45(S 01): 14-17
DOI: 10.1055/s-0042-103200
Schwerpunkt
© Georg Thieme Verlag Stuttgart · New York

Spezifische Antidote für nicht Vitamin-K-abhängige orale Antikoagulanzien – Aktueller Entwicklungsstand

NOAC specific antidotes – State of the art
Oliver Grottke
1   Klinik für Anästhesiologie, Experimentelle Hämostaseologie, Universitätsklinikum RWTH Aachen
› Author Affiliations
Further Information

Publication History

Publication Date:
03 May 2016 (online)

Orale Antikoagulanzien sind für die Schlaganfallprävention bei Vorhofflimmern sowie die Therapie und Prophylaxe venöser Thromboembolien unverzichtbar. In den letzten Jahren ist mit den nicht Vitamin-K-abhängigen oralen Antikoagulanzien (NOAKs) eine Wirkstoffgruppe in den Vordergrund gerückt, die hinsichtlich ihrer Wirksamkeit und Sicherheit gegenüber den klassischen Antikoagulanzien, wie Vitamin-K-Antagonisten, relevante Vorteile bietet. Blutungskomplikationen gehören jedoch nach wie vor zu den möglichen Nebenwirkungen. Mit der Entwicklung NOAK-spezifischer Antidote wird nun ein weiterer Fortschritt in der Sicherheit der antithrombotischen Therapie erzielt: Mit Idarucizumab ist bereits ein spezifisch und rasch wirksames Antidot gegen den direkten Thrombininhibitor Dabigatran auf dem Markt verfügbar. Zur Wirkungsaufhebung der Faktor-Xa-Inhibitoren ist Andexanet alfa in Phase III der klinischen Entwicklung.

Oral anticoagulants have become indispensable for the prevention of stroke in patients with atrial fibrillation and the therapy and prevention of venous thromboembolism. Over the past years, the group of NOAC came to the fore, which bears several advantages compared to conventional vitamin k antagonists. Nevertheless, bleeding complications are a possible side effect of these therapeutic agents. The development of NOAC specific antidotes can potentially improve safety in antithrombotic therapy. Idarucizumab, an antidote specifically designed for the reversal of the direct thrombin inhibitor dabigatran already underwent approval and was brought to the market. A reversal agent for factor Xa anticoagulants, andexanet alfa, is currently under clinical investigation (phase III).

 
  • Literatur

  • 1 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
  • 2 Connolly SJ, Wallentin L, Yusuf S. Additional events in the RE-LY trial. N Engl J Med 2014; 371: 1464-1465
  • 3 Camm AJ, Lip GY, De Caterina R et al. ESC Committee for Practice Guidelines-CPG. Document Reviewers 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Europace 2012; 14: 1385-1413
  • 4 Tamayo S, Frank Peacock W, Patel M et al. Characterizing major bleeding in patients with nonvalvular atrial fibrillation: a pharmacovigilance study of 27 467 patients taking rivaroxaban. Clinical Cardiology Clin Cardiol 2015; 38: 63-68
  • 5 Schiele F, van Ryn J, Canada K et al. A specific antidote for dabigatran: functional and structural characterization. Blood 2013; 121: 3554-3562
  • 6 Grottke O, Honickel M, van Ryn J et al. Idarucizumab, a Specific Dabigatran Reversal Agent, Reduces Blood Loss in a Porcine Model of Trauma With Dabigatran Anticoagulation. J Am Coll Cardiol 2015; 66: 1518-1519
  • 7 Honickel M, Treutler S, van Ryn J, Tillmann S, Rossaint R, Grottke O. Reversal of dabigatran anticoagulation ex vivo: Porcine study comparing prothrombin complex concentrates and idarucizumab. Thromb Haemost 2015; 113: 728-740
  • 8 Grottke O, van Ryn J, Spronk HM, Rossaint R. Prothrombin complex concentrates and a specific antidote to dabigatran are effective ex-vivo in reversing the effects of dabigatran in an anticoagulation/liver trauma experimental model. Crit Care 2014; 18
  • 9 Glund S, Stangier J, Schmohl M et al. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial. Lancet S0140-6736(15)60732-2 2015;
  • 10 Glund S, Stangier J, Schohl M et al. Idarucizumab, a Specific Antidote for Dabigatran: Immediate, Complete and Sustained Reversal of Dabigatran Induced Anticoagulation in Elderly and Renally Impaired Subjects. Oral Presentation at The 56th American Society of Hematology Annual Meeting & Exposition, San Francisco, USA, 8 December 2014. Blood Abstract 344 2014; 124
  • 11 Pollack CV, Reilly PA, Bernstein R et al. Design and rationale for RE-VERSE AD: A phase 3 study of idarucizumab, a specific reversal agent for dabigatran. Thromb Haemost 2015; 114: 198-205
  • 12 Pollack CV, Reilly PA, Eikelboom J et al. Idarucizumab for Dabigatran Reversal (RE-VERSE AD). N Engl J Med 2015; 373: 511-520
  • 13 Grottke O, Fries D, Nascimento B. Perioperatively acquired disorders of coagulation. Curr Opin Anaesthesiol 2015; 28: 113-122
  • 14 Connors JM. Antidote for Factor Xa Anticoagulants. N Engl J Med 2015; 373: 2471-2472
  • 15 Siegal DM, Curnutte JT, Connolly SJ et al. Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. N Engl J Med 2015; 373: 2413-2424
  • 16 Ansell JE, Bakhru SH, Laulicht BE et al. Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med 2014; 371: 2141-2142