Vol 57, No 6 (2023)
Research Paper
Published online: 2023-11-13

open access

Page views 748
Article views/downloads 512
Get Citation

Connect on Social Media

Connect on Social Media

Reversing dabigatran effect with idarucizumab to enable intravenous thrombolysis in patients with acute ischaemic stroke — a single centre experience

Ewa Włodarczyk1, Katarzyna Sawczyńska12, Paweł Wrona12, Agnieszka Słowik12
Pubmed: 37955597
Neurol Neurochir Pol 2023;57(6):465-476.

Abstract

Introduction. Our study analysed the safety and effectiveness of idarucizumab in enabling intravenous thrombolysis (IVT) in dabigatran-treated patients with acute ischaemic stroke (AIS).

Clinical rationale for the study. New oral anticoagulants (NOAC), including dabigatran, are the first-choice treatment option for preventing ischaemic stroke in patients with non-valvular atrial fibrillation (AF). However, a significant percentage of AF patients develops AIS despite NOAC treatment. According to current guidelines, treatment with IVT is contraindicated in patients who have received NOAC within the last 48 hours. Idarucizumab is a fragment of a monoclonal antibody that reverses the anticoagulation effect of dabigatran. The latest research shows that it can enable safe and successful IVT in patients with recent dabigatran intake, but more data is needed to confirm the safety and effectiveness of such treatment.

Material and methods. Our study included dabigatran-treated patients who received idarucizumab to allow AIS treatment with IVT in the University Hospital in Kraków (Poland) from December 2018 to June 2023. We gathered data on their past medical history, stroke severity, course of treatment and outcomes as defined by modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS) scores at discharge. A good functional outcome was defined as mRS 0–2 points at discharge.

Results. This observational study included 19 patients (13 male and six female) with a median age of 74 (IQR = 13) years. In all patients (100%), the reason for dabigatran treatment was AF. A good functional outcome after treatment (mRS 0–2) was achieved in 68.4% of patients, but mRS was already ≥ 3 points before stroke onset in three (15.8%) patients. Haemorrhagic transformation of stroke occurred in three (15.8%) patients, including symptomatic intracranial haemorrhage in two (10.5%). The mortality rate was 5.3%.

Conclusions and clinical implications. Our study results are in line with previous research on this topic, showing that IVT after idarucizumab can be successfully administered and is reasonably safe in dabigatran-treated patients with AIS.

Article available in PDF format

View PDF Download PDF file

References

  1. Katan M, Luft A. Global Burden of Stroke. Semin Neurol. 2018; 38(2): 208–211.
  2. Khatri P, Abruzzo T, Yeatts SD, et al. IMS I and II Investigators. Good clinical outcome after ischemic stroke with successful revascularization is time-dependent. Neurology. 2009; 73(13): 1066–1072.
  3. Saraiva JF. Stroke Prevention with Oral Anticoagulants: Summary of the Evidence and Efficacy Measures as an Aid to Treatment Choices. Cardiol Ther. 2018; 7(1): 15–24.
  4. Bang OhY, Park KM, Jeong DS. Occurrence of Ischemic Stroke in Patients With Atrial Fibrillation Receiving Non-Vitamin K Oral Anticoagulants: Causes and Prevention Strategies. J Stroke. 2023; 25(2): 199–213.
  5. Berge E, Whiteley W, Audebert H, et al. European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke. Eur Stroke J. 2021; 6(1): I–LXII.
  6. Pollack CV, Reilly PA, van Ryn J, et al. Idarucizumab for Dabigatran Reversal — Full Cohort Analysis. N Engl J Med. 2017; 377(5): 431–441.
  7. Cosentino F, Grant PJ, Aboyans V, et al. ESC Scientific Document Group. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020; 41(2): 255–323.
  8. Zhang Y, Song S, Li Z, et al. The Application of Software "Rapid Processing of Perfusion and Diffusion" in Acute Ischemic Stroke. Brain Sci. 2022; 12(11).
  9. Morinaga Y, Nii K, Takemura Y, et al. Types of intraparenchymal hematoma as a predictor after revascularization in patients with anterior circulation acute ischemic stroke. Surg Neurol Int. 2021; 12: 102.
  10. Hindricks G, Potpara T, Dagres N, et al. ESC Scientific Document Group. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021; 42(5): 373–498.
  11. Hankey GJ, Norrving Bo, Hacke W, et al. Management of acute stroke in patients taking novel oral anticoagulants. Int J Stroke. 2014; 9(5): 627–632.
  12. Auer E, Frey S, Kaesmacher J, et al. Stroke severity in patients with preceding direct oral anticoagulant therapy as compared to vitamin K antagonists. J Neurol. 2019; 266(9): 2263–2272.
  13. Eikelboom J, Quinlan D, Ryn Jv, et al. Idarucizumab. Circulation. 2015; 132(25): 2412–2422.
  14. Cuker A, Burnett A, Triller D, et al. Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum. Am J Hematol. 2019; 94(6): 697–709.
  15. Błażejewska-Hyżorek B, Czernuszenko A, Członkowska A, et al. Wytyczne postępowania w udarze mózgu. Polski Przegląd Neurologiczny. 2019; 15(A): 1–156.
  16. Ohya Y, Makihara N, Wakisaka K, et al. Thrombolytic therapy in severe cardioembolic stroke after reversal of dabigatran with idarucizumab: case report and literature review. J Stroke Cerebrovasc Dis. 2018; 27(7): e128–e131.
  17. Lin YT, Lai YJ, Lai TH. Idarucizumab for intravenous thrombolysis and endovascular thrombectomy in acute stroke: a case report. J Emerg Med. 2020; 58(3): e113–e116.
  18. Baule A, Cabigiosu F, Zanda B, et al. Thrombolysis in Acute Ischemic Stroke after Idarucizumab for Dabigatran Etexilate Reversal in Elderly: A Case Report. J Vasc Interv Neurol. 2018; 10(2): 15–17.
  19. Xie D, Wang X, Li Y, et al. Intravenous thrombolysis after reversal of dabigatran with idarucizumab in acute ischemic stroke: a case report. Front Aging Neurosci. 2021; 13: 765037.
  20. Bissig D, Manjunath R, Traylor BR, et al. Acute stroke despite dabigatran anticoagulation treated with idarucizumab and intravenous tissue plasminogen activator. J Stroke Cerebrovasc Dis. 2017; 26(6): e102–e104.
  21. Harsha KJ, Thirunavukkarasu S, Butcher K. Acute stroke thrombolysis following dabigatran reversal using idarucizumab. Neurol India. 2019; 67(2): 568–570.
  22. Meyer D, Chu F, Derry K, et al. Acute reversal of dabigatran with Idarucizumab for intravenous thrombolysis as acute stroke treatment. J Clin Neurosci. 2019; 59: 355–357.
  23. Loh CH, Herkes G. Republished: Successful thrombolysis for acute ischaemic stroke after reversal of dabigatran etexilate with idarucizumab. Drug Ther Bull. 2019; 57(9): 141–143.
  24. Vukorepa G, Deveđija S, Crnjaković M, et al. Successful intravenous thrombolysis in acute ischemic stroke after reversal of dabigatran etexilate with idarucizumab at the end of therapeutic time window. Turk J Emerg Med. 2020; 20(2): 90–92.
  25. Tireli D, He J, Nordling MM, et al. Systemic thrombolysis in acute ischemic stroke after dabigatran etexilate reversal with idarucizumab — a case report. J Stroke Cerebrovasc Dis. 2017; 26(7): e123–e125.
  26. Pásztor M, Bereczki D, Szakács Z, et al. Idarucizumab adását követően elvégzett szisztémás thrombolysis akut ischaemiás stroke-ban. Ideggyógyászati szemle. 2017; 70(7-8): 284–288.
  27. Hieber M, Bardutzky J. Immediate Reversal of Dabigatran by Idarucizumab Prior to Laboratory and Imaging Results in Acute Stroke. Front Neurol. 2019; 10: 230.
  28. Hosoki S, Takagi M, Yamagami H, et al. Paradoxical elevation of plasma dabigatran after reversal with idarucizumab in stroke thrombolysis. J Neurol. 2018; 265(10): 2451–2453.
  29. Alvarez Bravo G, Orts Castro E, Carvalho Monteiro G, et al. Intravenous fibrinolysis in ischemic stroke of large vessel after reversing effect of dabigatran with idarucizumab. J Stroke Cerebrovasc Dis. 2017; 26(9): e192–e193.
  30. Jala S, O'Brien E. Treatment with intravenous alteplase for acute ischemic stroke after reversal of dabigatran with idarucizumab: a case study. J Neurosci Nurs. 2019; 51(1): 21–25.
  31. Wowern Fv, Brizzi M, Holst J. Reversal of the Anticoagulation Effects of Dabigatran Etexilate by Idarucizumab in Three Patients Needing Urgent Surgical Intervention and One Case of Intravenous Thrombolysis in Ischaemic Stroke. Eur J Case Rep Intern Med. 2017; 4(4): 000569.
  32. Binet Q, Hammer FD, Rocrelle O, et al. Systemic thrombolysis and endovascular thrombectomy in severe acute ischemic stroke after dabigatran reversal with idarucizumab. Clin Case Rep. 2018; 6(4): 698–701.
  33. Agosti S, Casalino L, Rocci E, et al. Successful intravenous thrombolysis for ischemic stroke after reversal of dabigatran anticoagulation with idarucizumab: a case report. J Med Case Rep. 2017; 11(1): 224.
  34. Mutzenbach JS, Pikija S, Otto F, et al. Intravenous thrombolysis in acute ischemic stroke after dabigatran reversal with idarucizumab - a case report. Ann Clin Transl Neurol. 2016; 3(11): 889–892.
  35. Ohtani T, Sintoku R, Yajima T, et al. Successful thrombolytic therapy with recombinant tissue plasminogen activator in ischemic stroke after idarucizumab administration for reversal of dabigatran: a case report. J Med Case Rep. 2019; 13(1): 390.
  36. Vene N, Mavri A, Božič-Mijovski M, et al. Idarucizumab for dabigatran reversal in daily clinical practice: A case series. Eur J Anaesthesiol. 2020; 37(10): 874–878.
  37. Schäfer N, Müller A, Wüllner U. Systemic thrombolysis for ischemic stroke after antagonizing dabigatran with idarucizumab-a case report. J Stroke Cerebrovasc Dis. 2016; 25(8): e126–e127.
  38. Lo WT, Ng KF, Chan SCh, et al. Intravenous stroke thrombolysis after reversal of dabigatran effect by idarucizumab: first reported case in Hong Kong. Hong Kong Med J. 2018; 24(1): 81–83.
  39. Berrouschot J, Stoll A, Hogh T, et al. Intravenous thrombolysis with recombinant tissue-type plasminogen activator in a stroke patient receiving dabigatran anticoagulant after antagonization with idarucizumab. Stroke. 2016; 47(7): 1936–1938.
  40. Haastrup SB, Hellfritzsch M, Nybo M, et al. Real-world experience with reversal of dabigatran by idarucizumab. Thromb Res. 2021; 197: 179–184.
  41. Schulz JG, Kreps B. Idarucizumab elimination of dabigatran minutes before systemic thrombolysis in acute ischemic stroke. J Neurol Sci. 2016; 370: 44.
  42. Laxamana LC, Co CO, Yu JR, et al. Dabigatran reversal with idarucizumab preceding thrombolysis in an octogenarian patient with chronic kidney disease and acute stroke: a case report. Clin Ther. 2020; 42(9): 1840–1845.
  43. Gawehn A, Ayari Y, Heuschkel C, et al. Successful thrombolysis with recombinant tissue plasminogen activator after antagonizing dabigatran by idarucizumab: a case report. J Med Case Rep. 2016; 10(1): 269.
  44. Turine G, Peeters A, Hermans C, et al. Intravenous thrombolysis after reversal of dabigatran by idarucizumab: a moment to be a pioneer. Acta Neurol Belg. 2017; 117(3): 753–755.
  45. Kikule I, Baborikina A, Haritoncenko I, et al. Idarucizumab in dabigatran-treated patients with acute ischemic stroke receiving thrombolytic therapy. Medicina (Kaunas). 2022; 58(10).
  46. Kermer P, Eschenfelder CC, Diener HC, et al. Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or intracranial hemorrhage in Germany - A national case collection. Int J Stroke. 2017; 12(4): 383–391.
  47. Kermer P, Eschenfelder CC, Diener HC, et al. Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or intracranial hemorrhage in Germany — A national case collection. Int J Stroke. 2017; 12(4): 383–391.
  48. Fang CW, Tsai YT, Chou PC, et al. Intravenous thrombolysis in acute ischemic stroke after idarucizumab reversal of dabigatran effect: analysis of the cases from taiwan. J Stroke Cerebrovasc Dis. 2019; 28(3): 815–820.
  49. Pretnar Oblak J, Sabovic M, Frol S. Intravenous thrombolysis after idarucizumab application in acute stroke patients-a potentially increased sensitivity of thrombi to lysis? J Stroke Cerebrovasc Dis. 2019; 28(3): 768–773.
  50. Hieber M, Hollasch H, Heck D, et al. Reversal of dabigatran using idarucizumab: single center experience in four acute stroke patients. J Thromb Thrombolysis. 2018; 46(1): 12–15.
  51. Šaňák D, Jakubíček S, Černík D, et al. Intravenous thrombolysis in patients with acute ischemic stroke after a reversal of dabigatran anticoagulation with idarucizumab: a real-world clinical experience. J Stroke Cerebrovasc Dis. 2018; 27(9): 2479–2483.
  52. Tsai LK, Lin HJ, Chua SK, et al. Real-world experience with idarucizumab to reverse anticoagulant effect in dabigatran-treated patients: report of 11 cases from taiwan. J Stroke Cerebrovasc Dis. 2018; 27(2): e27–e33.
  53. Vosko MR, Bocksrucker C, Drwiła R, et al. Real-life experience with the specific reversal agent idarucizumab for the management of emergency situations in dabigatran-treated patients: a series of 11 cases. J Thromb Thrombolysis. 2017; 43(3): 306–317.
  54. Amin S, Kasischke KA, Elsayed K, et al. No time to lose: cases of anticoagulant reversal before thrombolysis in acute ischemic stroke patients. Cureus. 2022; 14(1): e21406.
  55. Amin S, Kasischke KA, Elsayed K, et al. No time to lose: cases of anticoagulant reversal before thrombolysis in acute ischemic stroke patients. Cureus. 2022; 14(1): e21406.
  56. Giannandrea D, Caponi C, Mengoni A, et al. Intravenous thrombolysis in stroke after dabigatran reversal with idarucizumab: case series and systematic review. J Neurol Neurosurg Psychiatry. 2019; 90(5): 619–623.
  57. Maramattom BV, Thomas J. Reversal of anticoagulation effect of dabigatran with idarucizumab, for thrombolysis in acute ischemic stroke: inimicus inimico amicus. Ann Indian Acad Neurol. 2019; 22(4): 515–517.
  58. Zhao H, Coote S, Pesavento L, et al. Prehospital idarucizumab prior to intravenous thrombolysis in a mobile stroke unit. Int J Stroke. 2019; 14(3): 265–269.
  59. Beharry J, Waters MJ, Drew R, et al. Dabigatran reversal before intravenous tenecteplase in acute ischemic stroke. Stroke. 2020; 51(5): 1616–1619.
  60. Kafke W, Kraft P. Intravenous thrombolysis after reversal of dabigatran by idarucizumab: a case report. Case Rep Neurol. 2016; 8(2): 140–144.
  61. Ng FC, Bice J, Rodda A, et al. Adverse clinical outcomes after dabigatran reversal with idarucizumab to facilitate acute stroke thrombolysis. J Neurol. 2017; 264(3): 591–594.
  62. Tsai YT, Hsiao YJ, Tsai LK, et al. Idarucizumab-facilitated intravenous thrombolysis in acute stroke with dabigatran: Two cases with hemorrhagic transformation. J Neurol Sci. 2018; 388: 155–157.
  63. Frol S, Sagris D, Pretnar Oblak J, et al. Intravenous Thrombolysis After Dabigatran Reversal by Idarucizumab: A Systematic Review of the Literature. Front Neurol. 2021; 12: 666086.
  64. Romoli M, Matteo E, Migliaccio L, et al. Thrombolysis after dabigatran reversal: A nation-wide Italian multicentre study, systematic review and meta-analysis. Eur Stroke J. 2023; 8(1): 117–124.
  65. Frol S, Sernec LP, Hudnik LK, et al. Idarucizumab reversal of dabigatran in patients with acute ischemic stroke and intracranial hemorrhage: comparison with non-idarucizumab-treated patients. CNS Drugs. 2021; 35(2): 233–242.
  66. van der Horst SFB, Martens ESL, den Exter PL, et al. Idarucizumab for dabigatran reversal: a systematic review and meta-analysis of indications and outcomes. Thromb Res. 2023; 228: 21–32.



Neurologia i Neurochirurgia Polska