Intravenous Thrombolysis in Patients With Ischemic Stroke and Recent Ingestion of Direct Oral Anticoagulants-Reference-Cited by-同舟云学术

Intravenous Thrombolysis in Patients With Ischemic Stroke and Recent Ingestion of Direct Oral Anticoagulants

Published:2023-03-01 Issue:3 Volume:80 Page:233
ISSN:2168-6149
Container-title:JAMA Neurology
language:en
Short-container-title:JAMA Neurol

Author:

Meinel Thomas R.¹,Wilson Duncan²³,Gensicke Henrik⁴⁵,Scheitz Jan F.⁶⁷⁸,Ringleb Peter⁹,Goganau Ioana⁹,Kaesmacher Johannes¹⁰,Bae Hee-Joon¹¹,Kim Do Yeon¹¹,Kermer Pawel¹²¹³,Suzuki Kentaro¹⁴,Kimura Kazumi¹⁴,Macha Kosmas¹⁵,Koga Masatoshi¹⁶,Wada Shinichi¹⁶,Altersberger Valerian⁴,Salerno Alexander¹⁷,Palanikumar Logesh¹⁸,Zini Andrea¹⁹,Forlivesi Stefano¹⁹,Kellert Lars²⁰,Wischmann Johannes²⁰,Kristoffersen Espen S.²¹²²,Beharry James²³,Barber P. Alan²⁴,Hong Jae Beom²⁴,Cereda Carlo²⁵,Schlemm Eckhard²⁶,Yakushiji Yusuke²⁷,Poli Sven²⁸²⁹,Leker Ronen³⁰,Romoli Michele³¹,Zedde Marialuisa³²,Curtze Sami³³,Ikenberg Benno³⁴,Uphaus Timo³⁵,Giannandrea David³⁶,Portela Pere Cardona³⁷,Veltkamp Roland⁹³⁸³⁹,Ranta Annemarei⁴⁰⁴¹,Arnold Marcel¹,Fischer Urs¹⁴,Cha Jae-Kwan⁴²,Wu Teddy Y.²³,Purrucker Jan C.⁹,Seiffge David J.¹,Goeldlin Martina⁴³,Siepen Bernhard⁴³,Mueller Madlaine⁴³,Beyeler Morin⁴³,Scutelnic Adrian⁴³,Jung Simon⁴³,Mujanovic Adnan⁴³,Kurmann Christoph⁴³,Dobrocky Tomas⁴³,Piechoviak Eike⁴³,Wiest Roland⁴³,Hakim Arsany⁴³,Bücke Philipp⁴³,Jana Zarzitzky⁴³,Carmen Lichti⁴³,Diana Isabella Dmytrow⁴³,Ramos João Nuno⁴³,Strambo Davide⁴³,Buehrer Menuela⁴³,Simaan Naaem⁴³,Honig Asaf⁴³,Filioglo Andrei⁴³,Grisendi Ilaria⁴³,Ferri Laura⁴³,Trapasso Maria Claudia⁴³,Benini Matteo⁴³,Pascarella Rosario⁴³,Moratti Claudio⁴³,Napoli Manuela⁴³,Sumaria Sheetal⁴³,Gröschel Klaus⁴³,Hahn Marianne⁴³,Polymeris Alexandros⁴³,Traenka Christopher⁴³,Zietz Annaelle⁴³,Lyrer Philippe⁴³,DeMarchis Gian Marco⁴³,Thilemann Sebastian⁴³,Piot Ines⁴³,Enz Lukas⁴³,Peters Nils⁴³,Katan Mira⁴³,Brehm Alexander⁴³,Psychogios Marios⁴³,Prange Ulrike⁴³,Spratt Neil⁴³,Roten Laurent⁴³,Chew BL Alvin⁴³,Stefela Jakub⁴³,von Rennenberg Regina⁴³,Litmeier Simon⁴³,Riegler Christoph⁴³,Klammer Markus⁴³,Erdur Hebun⁴³,Simon Hellwig⁴³,Mauro Magoni⁴³,Marco Longoni⁴³,Francesco Cordici⁴³,Sara Biguzzi⁴³,Tan Peter⁴³,Ercegovac Marko⁴³,Berisavac Ivana⁴³,Haupenthal David⁴³,Gassmann Luise⁴³,Marsch Armin⁴³,Siedler Gabriela⁴³,Weir Louise⁴³,Pesavento Lauren⁴³,Yassi Nawaf⁴³,Davis Stephen⁴³,Ip Bonaventure⁴³,Leung Thomas⁴³,Gomez-Exposito Alexandra⁴³,Mbroh Joshua⁴³,Tünnerhoff Johannes⁴³,Barbu Gabriel⁴³,Wang Yi⁴³,Mengel Annerose⁴³,Katharina Feil⁴³,Kowarik Markus⁴³,Ziemann Ulf⁴³,Kim Jun Yup⁴³,Kang Jihoon⁴³,Han Moon-Ku⁴³,Kim Beom Joon⁴³,Choi Kang-Ho⁴³,Park Man-Seok⁴³,Cho Ki-Hyun⁴³,Kim Joon-Tae⁴³,Shin Dong-Ick⁴³,Yum Kyu Sun⁴³,Kim Dae-Hyun⁴³,Cha Jae-Kwan⁴³,Park Jong-Moo⁴³,Kang Kyusik⁴³,Kim Yong Soo⁴³,Kim Jae Guk⁴³,Lee Soo Joo⁴³,Oh Mi-Sun⁴³,Lee Byung-Chul⁴³,Lee Minwoo⁴³,Yu Kyung-Ho⁴³,Park Hong-Kyun⁴³,Hong Keun-Sik⁴³,Cho Yong-Jin⁴³,Choi Jay Chol⁴³,Kim Joong-Goo⁴³,Kang Chul-Hoo⁴³,Sohn Sung Il⁴³,Hong Jeong-Ho⁴³,Jang Seong Hwa⁴³,Park Hyungjong⁴³,Park Tai Hwan⁴³,Park Sang-Soon⁴³,Lee Kyung Bok⁴³,Kwon Jee-Hyun⁴³,Kim Wook-Joo⁴³,Lee Jun⁴³,Kwon Doo Hyuk⁴³,Gwak Dong-Seok⁴³,Kim Dong-Eog⁴³,Lee Keon-Joo⁴³,Lee Sang-Hwa⁴³,Kim Chulho⁴³,Jeong Hae-Bong⁴³,Park Kwang Yeol⁴³,Lee Ji Sung⁴³,Lee Juneyoung⁴³,Martinez-Majander Nicolas⁴³,Sibolt Gerli⁴³,Tiainen Marjaana⁴³,Gentile Mauro⁴³,Migliaccio Ludovica⁴³,Simonetti Luigi⁴³,Paolucci Matteo⁴³,Flores Alan⁴³,Seró Laia⁴³,Turc Guillaume⁴³,Oppenheim Catherine⁴³,Naggara Olivier⁴³,Ben Hassen Wagih⁴³,Benzakoun Joseph⁴³,Yakushiji Yusuke⁴³,Kunieda Takenobu⁴³,Kägi Georg¹⁴⁴,Engelter Stefan⁴⁵,Nolte Christian H.⁶⁸⁴⁵⁴⁶⁴⁷,Kallmünzer Bernd¹⁵,Michel Patrik¹⁷,Kleinig Timothy J.¹⁸,Fink John⁴⁸,Rønning Ole Morten²¹,Campbell Bruce²³,Nederkoorn Paul J.⁴⁹,Thomalla Götz²⁶,Kunieda Takenobu²⁷,Poli Khouloud²⁸²⁹,Béjot Yannick⁵⁰,Soo Yannie⁵¹,Garcia-Esperon Carlos⁵²⁵³,Ntaios Georges⁵⁴,Cordonnier Charlotte⁵⁵,Marto João Pedro⁵⁶,Bigliardi Guido⁵⁷,Lun François⁵⁸,Choi Philip M. C.⁵⁹,Steiner Thorsten⁶⁰⁶¹,Ustrell Xavier⁶²,Werring David⁶³,Wegener Susanne⁶⁴,Pezzini Alessandro⁶⁵,Du Houwei⁶⁶⁶⁷,Martí-Fàbregas Joan⁶⁸,Cánovas-Vergé David⁶⁹,Strbian Daniel⁷⁰,Padjen Visnja⁷¹,Yaghi Shadi⁷²,Stretz Christoph⁷²,Kim Joon-Tae⁷³, ,

Affiliation:

1. Stroke Research Center Bern, Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Switzerland

2. Department of Neurology, Christchurch Hospital, Christchurch, New Zealand

3. New Zealand Brain Research Institute, Christchurch, New Zealand

4. Stroke Center, Department of Neurology, University Hospital Basel, Basel, Switzerland

5. Neurology and Neurorehabilitation, University Department of Geriatric Medicine Felix Platter, University of Basel, Basel, Switzerland

6. Department of Neurology, Berlin Institute of Health, Charité–Universitätsmedizin Berlin, Berlin, Germany

7. German Center for Cardiovascular Research Partner Site Berlin, Germany

8. Center for Stroke Research Berlin, Charité–Universitätsmedizin Berlin, Berlin, Germany

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

10. Institute of Diagnostic and Interventional Neuroradiology, Stroke Research Center Bern, Inselspital, Bern University Hospital, University of Bern, Switzerland

11. Department of Neurology, Cerebrovascular Disease Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, South Korea

12. Department of Neurology, Friesland Kliniken, Sande, Germany

13. Department of Neurology, University Medicine Göttingen, Göttingen, Germany

14. Department of Neurology, Nippon Medical School, Tokyo, Japan

15. Department of Neurology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

16. Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan

17. Stroke Center, Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

18. Department of Neurology, Royal Adelaide Hospital, Adelaide, Australia

19. IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Department of Neurology and Stroke Center, Maggiore Hospital, Bologna, Italy

20. Department of Neurology, University Hospital, LMU Munich, Munich, Germany

21. Department of Neurology, Akershus University Hospital, Lørenskog, Norway

22. Department of General Practice, Institute of Health and Society (HELSAM), University of Oslo, Oslo, Norway

23. Department of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia

24. Department of Medicine, Auckland University, Auckland, New Zealand

25. Stroke Center and Department of Neurology, Neurocenter of Southern Switzerland, Lugano, Switzerland

26. Klinik und Poliklinik Für Neurologie, Kopf, und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

27. Department of Neurology Kansai Medical University, Hirakata, Japan

28. Department of Neurology and Stroke, University of Tübingen, Tübingen, Germany

29. Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany

30. Department of Neurology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

31. Neurology and Stroke Unit, Department of Neuroscience, Bufalini Hospital, Cesena, Italy

32. Neurology Unit, Stroke Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy

33. Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

34. Department of Neurology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

35. Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Germany

36. Division of Neurology and Stroke Unit, Department of Neurology, Gubbio and Città di Castello Hospital, Perugia, Italy

37. Department of Neurology, Stroke Unit, Hospital Universitari Bellvitge, Barcelona, Spain

38. Klinik für Neurologie, Alfried Krupp Krankenhaus, Essen, Germany

39. Department of Brain Sciences, Imperial College London, London, United Kingdom

40. Department of Medicine, University of Otago, Wellington, New Zealand

41. Department of Neurology, Capital and Coast District Health Board, Wellington, New Zealand

42. Department of Neurology, Dong-A University Hospital, Busan, South Korea

43. and the DOAC-IVT Writing Group

44. Department of Neurology, Cantonal Hospital, St Gallen, Switzerland

45. Berlin Institute of Health at Charité–Universitätsmedizin Berlin, Berlin, Germany

46. German Center for Cardiovascular Research Partner Site Berlin, Berlin, Germany

47. German Center for Neurodegenerative Diseases Partner Site Berlin, Berlin, Germany

48. Department of Neurology, Canterbury District Health Board, Christchurch, New Zealand

49. Department of Neurology, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, the Netherlands

50. Department of Neurology, University Hospital Dijon, Dijon, France

51. Division of Neurology, Department of Medicine and Therapeutics Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China

52. John Hunter Hospital, Newcastle, Australia

53. Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia

54. Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece

55. Lille Neuroscience and Cognition Research Center, INSERM, CHU Lille, Lille, France

56. Department of Neurology, Hospital de Egas Moniz, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal

57. Department of Neurology, University Hospital Modena, Modena, Italy

58. Department of Neurology, GHU Paris Psychiatrie et Neurosciences, Université de Paris, Paris, France

59. Department of Neuroscience, Eastern Health, Eastern Health Clinical School, Monash University, Melbourne, Australia

60. Department of Neurology, Klinikum Frankfurt Höchst, Frankfurt am Main, Germany

61. Department of Neurology, Universität Heidelberg, Heidelberg, Germany

62. Stroke Unit, Neurology Department, Hospital Universitari Joan XXIII, Tarragona, Spain

63. Stroke Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom

64. Department of Neurology, University Hospital Zurich, University of Zurich, Zurich, Switzerland

65. Department of Clinical and Experimental Sciences, Neurology Clinic, University of Brescia, Neurology Unit, ASST Spedali Civili, Brescia, Italy

66. Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China

67. Institute of Clinical Neurology, Fujian Medical University, Fuzhou, China

68. Stroke Unit, Department of Neurology, Institute of Biomedical Research Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

69. Neurology Department, Hospital Parc Tauli, Sabadell, Spain

70. Department of Neurology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland

71. Neurology Clinic, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

72. Department of Neurology, The Warren Alpert Medical School of Brown University, Providence, Rhode Island

73. Department of Neurology, Chonnam National University Hospital, Gwangju, South Korea

Abstract

ImportanceInternational guidelines recommend avoiding intravenous thrombolysis (IVT) in patients with ischemic stroke who have a recent intake of a direct oral anticoagulant (DOAC).ObjectiveTo determine the risk of symptomatic intracranial hemorrhage (sICH) associated with use of IVT in patients with recent DOAC ingestion.Design, Setting, and ParticipantsThis international, multicenter, retrospective cohort study included 64 primary and comprehensive stroke centers across Europe, Asia, Australia, and New Zealand. Consecutive adult patients with ischemic stroke who received IVT (both with and without thrombectomy) were included. Patients whose last known DOAC ingestion was more than 48 hours before stroke onset were excluded. A total of 832 patients with recent DOAC use were compared with 32 375 controls without recent DOAC use. Data were collected from January 2008 to December 2021.ExposuresPrior DOAC therapy (confirmed last ingestion within 48 hours prior to IVT) compared with no prior oral anticoagulation.Main Outcomes and MeasuresThe main outcome was sICH within 36 hours after IVT, defined as worsening of at least 4 points on the National Institutes of Health Stroke Scale and attributed to radiologically evident intracranial hemorrhage. Outcomes were compared according to different selection strategies (DOAC-level measurements, DOAC reversal treatment, IVT with neither DOAC-level measurement nor idarucizumab). The association of sICH with DOAC plasma levels and very recent ingestions was explored in sensitivity analyses.ResultsOf 33 207 included patients, 14 458 (43.5%) were female, and the median (IQR) age was 73 (62-80) years. The median (IQR) National Institutes of Health Stroke Scale score was 9 (5-16). Of the 832 patients taking DOAC, 252 (30.3%) received DOAC reversal before IVT (all idarucizumab), 225 (27.0%) had DOAC-level measurements, and 355 (42.7%) received IVT without measuring DOAC plasma levels or reversal treatment. The unadjusted rate of sICH was 2.5% (95% CI, 1.6-3.8) in patients taking DOACs compared with 4.1% (95% CI, 3.9-4.4) in control patients using no anticoagulants. Recent DOAC ingestion was associated with lower odds of sICH after IVT compared with no anticoagulation (adjusted odds ratio, 0.57; 95% CI, 0.36-0.92). This finding was consistent among the different selection strategies and in sensitivity analyses of patients with detectable plasma levels or very recent ingestion.Conclusions and RelevanceIn this study, there was insufficient evidence of excess harm associated with off-label IVT in selected patients after ischemic stroke with recent DOAC ingestion.

Publisher

American Medical Association (AMA)

Subject

Neurology (clinical)

Link

https://jamanetwork.com/journals/jamaneurology/articlepdf/2799622/jamaneurology_meinel_2023_oi_220085_1677854390.03366.pdf

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