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Neue orale direkte Antikoagulanzien

Viele Vorteile, aber offene Fragen

New direct oral anticoagulants

Many advantages, but open questions

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An Erratum to this article was published on 07 September 2014

Zusammenfassung

Das gesamte Feld der Antikoagulation ist seit einigen Jahren durch die Einführung der direkten oralen Antikoagulanzien in Bewegung geraten. Allen gemeinsam sind die stabile orale Bioverfügbarkeit, die im Vergleich zu Vitamin-K-Antagonisten kurze Halbwertszeit, die geringe Interaktion mit anderen Arzneimitteln und die fixe Dosierung ohne Laborkontrolle. Zwischen den einzelnen Präparaten gibt es aber Unterschiede in der Metabolisierung, der Beeinflussung der in der klinischen Routine gebräuchlichen Gerinnungsteste, der Möglichkeiten zur Bestimmung des jeweiligen Plasmaspiegels, und – von größter klinischer Bedeutung – der Dosierregime, der klinischen Evidenz und schließlich der Zulassung.

Die folgende Übersicht erläutert die pharmakologischen Eigenschaften, das klinische Indikationsspektrum, die verschiedenen Dosisregime, sowie ersten Erfahrungen aus dem praktischen Gebrauch. Jedes der vier Themen wird ergänzt durch eine Zusammenstellung und Diskussion noch offener Fragen. Die in Studien klar belegten Vorteile der direkten oralen Antikoagulanzien werden sich nur vollständig in die klinische Routine überführen lassen, wenn in strenger Befolgung der derzeit zugelassenen Indikations- und Dosiervorgaben kontrollierte Erfahrungen auf den noch offenen Feldern der Anwendung gemacht und mitgeteilt werden.

Abstract

In the past few years, the clinical field of anticoagulation has undergone dramatic changes due to the introduction of the new class of direct oral anticoagulants. All these agents share common features such as stable oral bioavailability, short half-life compared to vitamin K antagonists, paucity of drug–drug interactions, and fixed dosing without laboratory monitoring. However, the new agents differ regarding metabolism pathways, impact on routine clotting tests, availability of test systems for plasma concentration, and—of utmost clinical importance—dose regimens, clinical evidence, and approved indications.

The present review outlines pharmacologic properties, clinical indications, different dose regimens, and preliminary clinical experience from their use in daily practice. Each of the four topics will be complemented by a compilation and in-depth discussion of open questions and lessons still to learn. The well-documented benefits of the direct oral anticoagulants as documented in clinical trials will translate to routine clinical practice only if all the rules regarding dosing and indications are obeyed, and if the experience with these agents is captured and communicated in a controlled manner.

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Literatur

  1. Agnelli G, Buller HR, Cohen A et al (2013) Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 369:799–808

    Article  CAS  PubMed  Google Scholar 

  2. Agnelli G, Buller HR, Cohen A et al (2013) Apixaban for extended treatment of venous thromboembolism. N Engl J Med 368:699–708

    Article  CAS  PubMed  Google Scholar 

  3. Alexander JH, Lopes RD, James S et al (2011) Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med 365:699–708

    Article  CAS  PubMed  Google Scholar 

  4. Bauer KA (2013) Pros and cons of new oral anticoagulants. Hematology Am Soc Hematol Educ Program 2013:464–470

    Article  PubMed  Google Scholar 

  5. Bauersachs R, Berkowitz SD, Brenner B et al (2010) Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 363:2499–2510

    Article  CAS  PubMed  Google Scholar 

  6. Buller HR, Decousus H, Grosso MA et al (2013) Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 369:1406–1415

    Article  PubMed  Google Scholar 

  7. Buller HR, Prins MH, Lensin AW et al (2012) Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 366:1287–1297

    Article  PubMed  Google Scholar 

  8. Connolly SJ, Eikelboom J, Joyner C et al (2011) Apixaban in patients with atrial fibrillation. N Engl J Med 364:806–817

    Article  CAS  PubMed  Google Scholar 

  9. Connolly SJ, Ezekowitz MD, Yusuf S et al (2009) Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 361:1139–1151

    Article  CAS  PubMed  Google Scholar 

  10. Connolly SJ, Wallentin L, Ezekowitz MD et al (2013) The long-term multicenter observational study of dabigatran treatment in patients with atrial fibrillation (RELY-ABLE) study. Circulation 128:237–243

    Article  CAS  PubMed  Google Scholar 

  11. Eikelboom JW, Connolly SJ, Brueckmann M et al (2013) Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med 369:1206–1214

    Article  CAS  PubMed  Google Scholar 

  12. Eriksson BI, Borris LC, Friedman RJ et al (2008) Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 358:2765–2775

    Article  CAS  PubMed  Google Scholar 

  13. Eriksson BI, Dahl OE, Huo MH et al (2011) Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*). A randomised, double-blind, non-inferiority trial. Thromb Haemost 105:721–729

    Article  CAS  PubMed  Google Scholar 

  14. Eriksson BI, Dahl OE, Rosencher N et al (2007) Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost 5:2178–2185

    Article  CAS  PubMed  Google Scholar 

  15. Eriksson BI, Dahl OE, Rosencher N et al (2007) Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet 370:949–956

    Article  CAS  PubMed  Google Scholar 

  16. Giugliano RP, Ruff CT, Braunwald E et al (2013) Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 369:2093–2104

    Article  CAS  PubMed  Google Scholar 

  17. Granger CB, Alexander JH, McMurray JJ et al (2011) Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365:981–992

    Article  CAS  PubMed  Google Scholar 

  18. Heidbuchel H, Verhamme P, Alings M et al (2013) EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J 34:2094–2106

    Article  CAS  PubMed  Google Scholar 

  19. Heidbuchel H, Verhamme P, Alings M et al (2013) European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 15:625–651

    Article  PubMed  Google Scholar 

  20. Kakkar AK, Brenner B, Dahl OE et al (2008) Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet 372:31–39

    Article  CAS  PubMed  Google Scholar 

  21. Koscielny J, Beyer-Westendorf J, von HC et al (2012) Risk of bleeding and haemorrhagic complication with rivaroxaban – periprocedural management of haemostasis. Hamostaseologie 32:287–293

    Article  CAS  PubMed  Google Scholar 

  22. Lassen MR, Ageno W, Borris LC et al (2008) Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 358:2776–2786

    Article  CAS  PubMed  Google Scholar 

  23. Lassen MR, Gallus A, Raskob GE et al (2010) Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med 363:2487–2498

    Article  CAS  PubMed  Google Scholar 

  24. Lassen MR, Raskob GE, Gallus A et al (2010) Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet 375:807–815

    Article  CAS  PubMed  Google Scholar 

  25. Makris M, Van Veen JJ, Tait CR et al (2013) Guideline on the management of bleeding in patients on antithrombotic agents. Br J Haematol 160:35–46

    Article  CAS  PubMed  Google Scholar 

  26. Mega JL, Braunwald E, Wiviott SD et al (2012) Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 366:9–19

    Article  CAS  PubMed  Google Scholar 

  27. Patel MR, Mahaffey KW, Garg J et al (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365:883–891

    Article  CAS  PubMed  Google Scholar 

  28. Schulman S, Kakkar AK, Goldhaber SZ et al (2014) Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation 129:764–772

    Article  CAS  PubMed  Google Scholar 

  29. Schulman S, Kearon C, Kakkar AK et al (2009) Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 361:2342–2352

    Article  CAS  PubMed  Google Scholar 

  30. Schulman S, Kearon C, Kakkar AK et al (2013) Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med 368:709–718

    Article  CAS  PubMed  Google Scholar 

  31. Spannagl M, Bauersachs R, Debus ES et al (2012) Dabigatran therapy – perioperative management and interpretation of coagulation tests. Hamostaseologie 32:294–305

    Article  CAS  PubMed  Google Scholar 

  32. Turpie AG, Haas S, Kreutz R et al (2014) A non-interventional comparison of rivaroxaban with standard of care for thromboprophylaxis after major orthopaedic surgery in 17,701 patients with propensity score adjustment. Thromb Haemost 111:94–102

    Article  CAS  PubMed  Google Scholar 

  33. Turpie AG, Lassen MR, Davidson BL et al (2009) Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 373:1673–1680

    Article  CAS  PubMed  Google Scholar 

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Einhaltung ethischer Richtlinien

Interessenkonflikt. S. Haas und S. Schellong üben Berater- und Vortragtätigkeiten für die Firmen Boehringer Ingelheim, Bayer Health Care, Daiichi Sankyo, BMS und Pfizer aus. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Haas, S., Schellong, S. Neue orale direkte Antikoagulanzien. Internist 55, 537–546 (2014). https://doi.org/10.1007/s00108-013-3424-3

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  • DOI: https://doi.org/10.1007/s00108-013-3424-3

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