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

Meinel TR, Wilson D, Gensicke H, Scheitz JF, Ringleb P, Goganau I, Kaesmacher J, Bae HJ, Kim DY, Kermer P, Suzuki K, Kimura K, Macha K, Koga M, Wada S, Altersberger V, Salerno A, Palanikumar L, Zini A, Forlivesi S, Kellert L, Wischmann J, Kristoffersen E, Beharry J, Barber PA, Hong JB, Cereda C, Schlemm E, Yakushiji Y, Poli S, Leker R, Romoli M, Zedde M, Curtze S, Ikenberg B, Uphaus T, Giannandrea D, Portela PC, Veltkamp R, Ranta A, Arnold M, Fischer U, Cha JK, Wu TY, Purrucker JC, Seiffge DJ (2023)

Publication Type: Journal article

Publication year: 2023

Journal

DOI: 10.1001/jamaneurol.2022.4782

Abstract

IMPORTANCE International guidelines recommend avoiding intravenous thrombolysis (IVT) in patients with ischemic stroke who have a recent intake of a direct oral anticoagulant (DOAC). OBJECTIVE To determine the risk of symptomatic intracranial hemorrhage (sICH) associated with use of IVT in patients with recent DOAC ingestion. DESIGN, SETTING, AND PARTICIPANTS This 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. EXPOSURES Prior DOAC therapy (confirmed last ingestion within 48 hours prior to IVT) compared with no prior oral anticoagulation. MAIN OUTCOMES AND MEASURES The 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. RESULTS Of 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 RELEVANCE In this study, there was insufficient evidence of excess harm associated with off-label IVT in selected patients after ischemic stroke with recent DOAC ingestion.

Authors with CRIS profile

Involved external institutions

Universität Bern Switzerland (CH) Christchurch Hospital New Zealand (NZ) Universitätsspital Basel Switzerland (CH) Helsingin yliopisto / University of Helsinki Finland (FI) Charité - Universitätsmedizin Berlin Germany (DE) Universitätsklinikum Heidelberg Germany (DE) Seoul National University (SNU) / 서울대학교 Korea, Republic of (KR) Friesland Kliniken gGmbH Germany (DE) Nippon Medical School Japan (JP) National Cerebral and Cardiovascular Center Japan (JP) Université de Lausanne (UNIL) Switzerland (CH) Royal Adelaide Hospital Australia (AU) Ospedale Maggiore di Bologna Italy (IT) University of Otago New Zealand (NZ) Ludwig-Maximilians-Universität (LMU) Germany (DE) Akershus University Hospital / Akershus universitetssykehus (Ahus) Norway (NO) The University of Melbourne Australia (AU) University of Auckland New Zealand (NZ) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Kansai Medical University Japan (JP) Eberhard Karls Universität Tübingen Germany (DE) Hadassah Medical Center / מרכז רפואי הדסה‎‎ Israel (IL) Ospedale “M. Bufalini” di Cesena Italy (IT) Azienda Unità Sanitaria Locale die Reggio Emilia Italy (IT) Technische Universität München (TUM) Germany (DE) Johannes Gutenberg-Universität Mainz (JGU) Germany (DE) Bellvitge University Hospital / Hospital Universitari de Bellvitge Spain (ES) Dong-a University Korea, Republic of (KR)

How to cite

APA:

Meinel, T.R., Wilson, D., Gensicke, H., Scheitz, J.F., Ringleb, P., Goganau, I.,... Seiffge, D.J. (2023). Intravenous Thrombolysis in Patients With Ischemic Stroke and Recent Ingestion of Direct Oral Anticoagulants. JAMA Neurology. https://dx.doi.org/10.1001/jamaneurol.2022.4782

MLA:

Meinel, Thomas R., et al. "Intravenous Thrombolysis in Patients With Ischemic Stroke and Recent Ingestion of Direct Oral Anticoagulants." JAMA Neurology (2023).

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