Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or intracranial hemorrhage in Germany—Updated series of 120 cases

Author:

Kermer Pawel1ORCID,Eschenfelder Christoph C2ORCID,Diener Hans-Christoph3,Grond Martin4,Abdalla Yasser5,Abraham Alexej6,Althaus Katharina7,Becks Gebhard8,Berrouschot Jörg9,Berthel Jörg10,Bode Felix J.1112,Burghaus Lothar13,Cangür Hakan14,Daffertshofer Michael15,Edelbusch Sebastian16,Eggers Jürgen17,Gerlach Rüdiger18,Gröschel Klaus19,Große-Dresselhaus Florian16,Günther Albrecht20,Haase Claus G21,Haensch Carl-Albrecht22,Harloff Andreas23,Heckmann Joseph G24,Held Valentin25,Hieber Maren23,Kauert Andreas6,Kern Rolf26,Kerz Thomas27,Köhrmann Martin3,Kraft Peter2829,Kühnlein Peter30,Latta Jan31,Leinisch Elke32,Lenz Arne33,Leithner Christoph34,Neumann-Haefelin Tobias10,Mäurer Mathias35,Müllges Wolfgang29,Nolte Christian H36,Obermann Mark37,Partowi Someieh38,Patzschke Peer39,Poli Sven40,Pulkowski Ulrich41,Purrucker Jan42ORCID,Rehfeldt Torsten43,Ringleb Peter A42,Röther Joachim44,Rossi Raluca45,El-Sabassy Hazem46,Sauer Oliver47,Schackert Gabriele48,Schäfer Niklas11,Schellinger Peter D49,Schneider Andreas21,Schuppner Ramona50,Schwab Stefan51,Schwarte Olav52,Seitz Rüdiger J53,Senger Sebastian54,Shah Yogesh P55,Sindern Eckhart56,Sparenberg Paul57,Steiner Thorsten58,Szabo Kristina25,Urbanek Christian59,Sarnowksi Bettina von60,Weissenborn Karin50,Wienecke Peter61,Witt Karsten62,Wruck Robert15,Wunderlich Silke63

Affiliation:

1. Department of Neurology, Nordwestkrankenhaus Sanderbusch, Sande and Department of Neurology, University Medicine Göttingen, Göttingen, Germany

2. Medical Affairs Germany, Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim am Rhein, Germany

3. Department of Neurology, University Hospital, Essen, Germany

4. Department of Neurology, Siegen, Germany

5. Department of Neurosurgery, Nordwestkrankenhaus Sanderbusch, Sande, Germany

6. Department of Neurology, Evangelisches Krankenhaus Königin Elisabeth Herzberge, Berlin, Germany

7. Department of Neurology, University of Ulm, Ulm, Germany

8. Department of Neurology, Klinikum Itzehoe, Itzehoe, Germany

9. Department of Neurology, Klinikum Altenburger Land GmbH, Altenburg, Germany

10. Department of Neurology, Klinikum Fulda, Fulda, Germany

11. Department of Neurology, University Bonn, Bonn, Germany

12. Department of Neurology, German Center for Neurodegenerative Disease, Bonn, Germany

13. Department of Neurology, Heilig Geist-Krankenhaus, Köln, Germany

14. Department of Neurology, Klinikum Wolfsburg, Wolfsburg, Germany

15. Department of Neurology, Klinikum Mittelbaden, Rastatt, Germany

16. Department of Neurology, Herz-Jesu-Krankenhaus Hiltrup, Münster, Germany

17. Department of Neurology, Sana Kliniken Lübeck, Lübeck, Germany

18. Department of Neurosurgery, Helios Klinikum Erfurt, Erfurt, Germany

19. Department of Neurology, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany

20. Department of Neurology, University Jena, Jena, Germany

21. Department of Neurology and clinical Neurophysiology, Evangelische Kliniken Gelsenkirchen, Gelsenkirchen, Germany

22. Department of Neurology, Kliniken Maria-Hilf, Mönchengladbach, Germany

23. Department of Neurology and Neurophysiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

24. Department of Neurology, Klinikum Landshut, Landshut, Germany

25. Department of Neurology, Universitätsmedizin Mannheim, Mannheim, Germany

26. Department of Neurology, Klinikverbund Kempten-Oberallgäu, Kempten, Germany

27. Department of Neurosurgery, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany

28. Department of Neurology, Klinikum Main-Spessart, Lohr, Germany

29. Department of Neurology, University Hospital Würzburg, Würzburg, Germany

30. Department of Neurology, Regiomed-Kliniken, Coburg, Germany

31. Department of Neurology, Helios Klinik, Hildburghausen, Germany

32. Department of Neurology, Helios Klinikum, Erfurt, Germany

33. Department of Neurology, Sozialstiftung Bamberg, Bamberg, Germany

34. Department of Neurology, Campus Virchow-Klinikum, Charité, Berlin, Germany

35. Department of Neurology, Klinikum Würzburg Mitte, Würzburg, Germany

36. Department of Neurology, Campus Benjamin Franklin, Charité, Berlin, Germany

37. Center for Neurology, Asklepios Hospitals Schildautal, Seesen, Germany

38. Stroke Unit, Marienhaus Klinikum, Kreis Ahrweiler, Bad Neuenahr-Ahrweiler, Germany

39. Westküstenkliniken, Brunsbüttel, Germany

40. Department of Neurology with Focus on Neurovascular Diseases and Neurooncology and Hertie Institute for Clinical Brain Research, University Hospital Tübingen, Tübingen, Germany

41. Department of Neurology, imland Klinik, Rendsburg, Germany

42. Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany

43. Department of Neurology, Dietrich-Bonhoeffer-Klinikum, Neubrandenburg, Germany

44. Department of Neurology, Asklepios Klinik Altona, Hamburg, Germany

45. Department of Neurology, Main-Kinzig-Kliniken, Gelnhausen, Germany

46. Department of Neurology, Klinikum Lippe, Lemgo, Germany

47. Department of Neurology, Diakonie-Klinikum, Schwäbisch-Hall

48. Department of Neurosurgery, University Hospital Dresden, Dresden, Germany

49. Department of Neurology and Neurogeriatry, Johannes Wesling Klinikum Minden, University Hospital, Minden, Germany

50. Department of Neurology, Hannover Medical School, Hannover, Germany

51. Department of Neurology, University Hospital Erlangen, Erlangen, Germany

52. Department of Neurology, Kreiskliniken Altötting-Burghausen, Altötting, Germany

53. Department of Neurology, Centre of Neurology and Neuropsychiatry, LVR-Klinikum Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany

54. Department for Neurosurgery, Saarland University Hospital, Homburg, Germany

55. Department of Neurology, Klinikum Kassel, Kassel, Germany

56. Department for Neurology, Diakovere Friederikenstift, Hannover, Germany

57. Department for Neurology, BG Klinikum Unfallkrankenhaus Berlin, Berlin, Germany

58. Department of Neurology, Klinikum Frankfurt Höchst, Frankfurt, Germany

59. Department for Neurology, Klinikum Ludwigshafen, Ludwigshafen, Germany

60. Department of Neurology, University Medicine Greifswald, Greifswald, Germany

61. Department for Neurology, Asklepios Fachklinik Teupitz, Teupitz, Germany

62. Department for Neurology and Research Center Neurosensory Science, Carl von Ossietzky-University, Oldenburg, Germany

63. Department for Neurology, Klinikum rechts der Isar, TU München, München, Germany

Abstract

Background Idarucizumab is a monoclonal antibody fragment with high affinity for dabigatran reversing its anticoagulant effects within minutes. Thereby, patients with acute ischemic stroke who are on dabigatran treatment may become eligible for thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). In patients on dabigatran with intracerebral hemorrhage idarucizumab could prevent lesion growth. Aims To provide insights into the clinical use of idarucizumab in patients under effective dabigatran anticoagulation presenting with signs of acute ischemic stroke or intracranial hemorrhage. Methods Retrospective data collected from German neurological/neurosurgical departments administering idarucizumab following product launch from January 2016 to August 2018 were used. Results One-hundred and twenty stroke patients received idarucizumab in 61 stroke centers. Eighty patients treated with dabigatran presented with ischemic stroke and 40 patients suffered intracranial bleeding (intracerebral hemorrhage (ICH) in n = 27). In patients receiving intravenous thrombolysis with rt-PA following idarucizumab, 78% showed a median improvement of 7 points in National Institutes of Health Stroke Scale. No bleeding complications were reported. Hematoma growth was observed in 3 out of 27 patients with ICH. Outcome was favorable with a median National Institutes of Health Stroke Scale improvement of 4 points and modified Rankin score 0–3 in 61%. Six out of 40 individuals (15%) with intracranial bleeding died during hospital stay. Conclusion Administration of rt-PA after reversal of dabigatran activity with idarucizumab in case of acute ischemic stroke seems feasible, effective, and safe. In dabigatran-associated intracranial hemorrhage, idarucizumab appears to prevent hematoma growth and to improve outcome.

Publisher

SAGE Publications

Subject

Neurology

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