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

Author

Meinel, Thomas R., Wilson, Duncan, Gensicke, Henrik, Scheitz, Jan F., Ringleb, Peter, Goganau, Ioana, Kaesmacher, Johannes, Bae, Hee-Joon, Kim, Do Yeon, Kermer, Pawel, Suzuki, Kentaro, Kimura, Kazumi, Macha, Kosmas, Koga, Masatoshi, Wada, Shinichi, Altersberger, Valerian, Salerno, Alexander, Palanikumar, Logesh, Zini, Andrea, Forlivesi, Stefano, Kellert, Lars, Wischmann, Johannes, Kristoffersen, Espen S., Beharry, James, Barber, P. Alan, Hong, Jae Beom, Cereda, Carlo, Schlemm, Eckhard, Yakushiji, Yusuke, Poli, Sven, Leker, Ronen, Romoli, Michele, Zedde, Marialuisa, Curtze, Sami, Ikenberg, Benno, Uphaus, Timo, Giannandrea, David, Portela, Pere Cardona, Veltkamp, Roland, Ranta, Annemarei, Arnold, Marcel, Fischer, Urs, Cha, Jae-Kwan, Wu, Teddy Y., Purrucker, Jan C., Seiffge, David J., Kägi, Georg, Engelter, Stefan, Nolte, Christian H., Kallmünzer, Bernd, Michel, Patrik, Kleinig, Timothy J., Fink, John, Rønning, Ole Morten, Campbell, Bruce, Nederkoorn, Paul J., Thomalla, G. tz, Kunieda, Takenobu, Poli, Khouloud, Béjot, Yannick, Soo, Yannie, Garcia-Esperon, Carlos, Ntaios, Georges, Cordonnier, Charlotte, Marto, João Pedro, Bigliardi, Guido, Lun, François, Choi, Philip M. C., Steiner, Thorsten, Ustrell, Xavier, Werring, David, Wegener, Susanne, Pezzini, Alessandro, du, Houwei, Martí-Fàbregas, Joan, Cánovas-Vergé, David, Strbian, Daniel, Padjen, Visnja, Yaghi, Shadi, Stretz, Christoph, Kim, Joon-Tae, HUS Neurocenter, Neurologian yksikkö, Department of Neurosciences, Neurology, ACS - Atherosclerosis & ischemic syndromes, and ANS - Neurovascular Disorders

Subjects
Rivaroxaban, Plasma-levels, Idarucizumab, 3112 Neurosciences, Intracranial hemorrhage, Recanalization therapies, Endovascular treatment, Neurology (clinical), Reperfusion therapy, 3124 Neurology and psychiatry, Tissue-plasminogen activator, Dabigatran, Management
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.

Published
2023

2. Intravenous Thrombolysis 4.5–9 Hours After Stroke Onset: A Cohort Study from the TRISP Collaboration

Author

Altersberger, Valerian L; https://orcid.org/0000-0002-0610-9328, Sibolt, Gerli, Enz, Lukas S, Hametner, Christian, Scheitz, Jan F, Henon, Hilde, Bigliardi, Guido, Strambo, Davide, Martinez‐Majander, Nicolas, Stolze, Lotte J, Heldner, Mirjam R; https://orcid.org/0000-0002-3594-2159, Grisendi, Ilaria, Jovanovic, Dejana R, Bejot, Yannick, Pezzini, Alessandro; https://orcid.org/0000-0001-8629-3315, Leker, Ronen R, Kägi, Georg, Wegener, Susanne; https://orcid.org/0000-0003-4369-7023, Cereda, Carlo W; https://orcid.org/0000-0002-6479-1476, Ntaios, Georges, De Marchis, Gian Marco; https://orcid.org/0000-0002-0342-9780, Bonati, Leo H, Psychogios, Marios, Lyrer, Philippe, Räty, Silja; https://orcid.org/0000-0002-6921-0597, Tiainen, Marjaana, Wouters, Anke, Caparros, François, Heyse, Miriam, Erdur, Hebun; https://orcid.org/0000-0001-5383-9625, et al, Altersberger, Valerian L; https://orcid.org/0000-0002-0610-9328, Sibolt, Gerli, Enz, Lukas S, Hametner, Christian, Scheitz, Jan F, Henon, Hilde, Bigliardi, Guido, Strambo, Davide, Martinez‐Majander, Nicolas, Stolze, Lotte J, Heldner, Mirjam R; https://orcid.org/0000-0002-3594-2159, Grisendi, Ilaria, Jovanovic, Dejana R, Bejot, Yannick, Pezzini, Alessandro; https://orcid.org/0000-0001-8629-3315, Leker, Ronen R, Kägi, Georg, Wegener, Susanne; https://orcid.org/0000-0003-4369-7023, Cereda, Carlo W; https://orcid.org/0000-0002-6479-1476, Ntaios, Georges, De Marchis, Gian Marco; https://orcid.org/0000-0002-0342-9780, Bonati, Leo H, Psychogios, Marios, Lyrer, Philippe, Räty, Silja; https://orcid.org/0000-0002-6921-0597, Tiainen, Marjaana, Wouters, Anke, Caparros, François, Heyse, Miriam, Erdur, Hebun; https://orcid.org/0000-0001-5383-9625, and et al

Abstract

ObjectiveTo investigate the safety and effectiveness of intravenous thrombolysis (IVT) >4.5–9 hours after stroke onset, and the relevance of advanced neuroimaging for patient selection.MethodsProspective multicenter cohort study from the ThRombolysis in Ischemic Stroke Patients (TRISP) collaboration. Outcomes were symptomatic intracranial hemorrhage, poor 3‐month functional outcome (modified Rankin scale 3–6) and mortality. We compared: (i) IVT >4.5–9 hours versus 0–4.5 hours after stroke onset and (ii) within the >4.5–9 hours group baseline advanced neuroimaging (computed tomography perfusion, magnetic resonance perfusion or magnetic resonance diffusion‐weighted imaging fluid‐attenuated inversion recovery) versus non‐advanced neuroimaging.ResultsOf 15,827 patients, 663 (4.2%) received IVT >4.5–9 hours and 15,164 (95.8%) within 4.5 hours after stroke onset. The main baseline characteristics were evenly distributed between both groups. Time of stroke onset was known in 74.9% of patients treated between >4.5 and 9 hours. Using propensity score weighted binary logistic regression analysis (onset‐to‐treatment time >4.5–9 hours vs onset‐to‐treatment time 0–4.5 hours), the probability of symptomatic intracranial hemorrhage (OR$_{adjusted}$ 0.80, 95% CI 0.53–1.17), poor functional outcome (OR$_{adjusted}$ 1.01, 95% CI 0.83–1.22), and mortality (OR$_{adjusted}$ 0.80, 95% CI 0.61–1.04) did not differ significantly between both groups. In patients treated between >4.5 and 9 hours, the use of advanced neuroimaging was associated with a 50% lower mortality compared with non‐advanced imaging only (9.9% vs 19.7%; OR$_{adjusted}$ 0.51, 95% CI 0.33–0.79).InterpretationThis study showed no evidence in difference of symptomatic intracranial hemorrhage, poor outcome, and mortality in selected stroke patients treated with IVT between >4.5 and 9 hours after stroke onset compared with those treated within 4.5 hours. Advanced neuroimaging for patient selection was associated with lower mo

Published
2023

4. Maintenance of Acute Stroke Care Service During the COVID-19 Pandemic Lockdown.

Author

Altersberger VL, Stolze LJ, Heldner MR, Henon H, Martinez-Majander N, Hametner C, Nordanstig A, Zini A, Nannoni S, Gonçalves B, Nolte CH, Baumgartner P, Kastrup A, Papanagiotou P, Kägi G, Leker RR, Zedde M, Padovani A, Pezzini A, Padjen V, Cereda CW, Ntaios G, Bonati LH, Rinkel LA, Fischer U, Scheitz JF, Wegener S, Turc G, Michel P, Gentile M, Rentzos A, Ringleb PA, Curtze S, Cordonnier C, Arnold M, Nederkoorn PJ, Engelter ST, and Gensicke H

Subjects
Aged, Aged, 80 and over, Cardiology organization & administration, Cohort Studies, Critical Care, Europe epidemiology, Female, Humans, Male, Middle Aged, Pandemics, Physical Distancing, Registries, Severity of Illness Index, Stroke prevention & control, Thrombolytic Therapy, Time-to-Treatment, Treatment Outcome, COVID-19 epidemiology, Hospitalization, Stroke epidemiology, Stroke therapy
Abstract

[Figure: see text].

Published
2021
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