Benefit and risk of intravenous alteplase in patients with acute large vessel occlusion stroke and low ASPECTS

Gabriel Broocks, Rosalie McDonough, Matthias Bechstein, Uta Hanning, Caspar Brekenfeld, Fabian Flottmann, Helge Kniep, Marie Teresa Nawka, Milani Deb-Chatterji, Götz Thomalla, Peter Sporns, Leonard Ll Yeo, Benjamin Yq Tan, Anil Gopinathan, Andreas Kastrup, Maria Politi, Panagiotis Papanagiotou, Andre Kemmling, Jens Fiehler, Lukas Meyer, German Stroke Registry – Endovascular Treatment (GSR-ET), Gabriel Broocks, Rosalie McDonough, Matthias Bechstein, Uta Hanning, Caspar Brekenfeld, Fabian Flottmann, Helge Kniep, Marie Teresa Nawka, Milani Deb-Chatterji, Götz Thomalla, Peter Sporns, Leonard Ll Yeo, Benjamin Yq Tan, Anil Gopinathan, Andreas Kastrup, Maria Politi, Panagiotis Papanagiotou, Andre Kemmling, Jens Fiehler, Lukas Meyer, German Stroke Registry – Endovascular Treatment (GSR-ET)

Abstract

Background: The benefit of best medical treatment including intravenous alteplase (IVT) before mechanical thrombectomy (MT) in patients with acute ischemic stroke and extensive early ischemic changes on baseline CT remains uncertain. The purpose of this study was to evaluate the benefit of IVT for patients with low ASPECTS (Alberta Stroke Programme Early CT Score) compared with patients with or without MT.

Methods: This multicenter study pooled consecutive patients with anterior circulation acute stroke and ASPECTS≤5 to analyze the impact of IVT on functional outcome, and to compare bridging IVT with direct MT. Functional endpoints were the rates of good (modified Rankin Scale (mRS) score ≤2) and very poor (mRS ≥5) outcome at day 90. Safety endpoint was the occurrence of symptomatic intracranial hemorrhage (sICH).

Results: 429 patients were included. 290 (68%) received IVT and 168 (39%) underwent MT. The rate of good functional outcome was 14.4% (95% CI 7.1% to 21.8%) for patients who received bridging IVT and 24.4% (95% CI 16.5% to 32.2%) for those who underwent direct MT. The rate of sICH was significantly higher in patients with bridging IVT compared with direct MT (17.8% vs 6.4%, p=0.004). In multivariable logistic regression analysis, IVT was significantly associated with very poor outcome (OR 2.22, 95% CI 1.05 to 4.73, p=0.04) and sICH (OR 3.44, 95% CI 1.18 to 10.07, p=0.02). Successful recanalization, age, and ASPECTS were associated with good functional outcome.

Conclusions: Bridging IVT in patients with low ASPECTS was associated with very poor functional outcome and an increased risk of sICH. The benefit of this treatment should therefore be carefully weighed in such scenarios. Further randomized controlled trials are required to validate our findings.

Keywords: brain; stroke; thrombectomy; thrombolysis.

Conflict of interest statement

Competing interests: JF: research support from the German Ministry of Science and Education (BMBF), German Ministry of Economy and Innovation (BMWi), German Research Foundation (DFG), European Union (EU), Hamburgische Investitions-/Förderbank (IFB), Medtronic, Microvention, Philips, Stryker; consultancy appointments; Acandis, Bayer, Boehringer Ingelheim, Cerenovus, Covidien, Evasc Neurovascular, MD Clinicals, Medtronic, Medina, Microvention, Penumbra, Route92, Stryker, Transverse Medical; stock holdings for Tegus. Editorial Board member at JNIS. GT reports receiving consulting fees from Acandis, grant support and lecture fees from Bayer, lecture fees from Boehringer Ingelheim, BristolMyersSquibb/Pfizer, and Daiichi Sankyo, and consulting fees and lecture fees from Portola and Stryker. LLLY has received research support from National Medical Research Council (NMRC), Singapore and research support from Ministry of Health (MOH), Singapore. Consultancy from Stryker, J&J, See-mode. Stock holdings for Cereoflo. PP is consultant for Penumbra and Ab Medica.

© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Proportion of patients with sICH (symptomatic intracerebral hemorrhage; left) according to treatment with intravenous thrombectomy with alteplase (IVT) and mechanical thrombectomy (MT), and proportion of patients with good functional outcome, defined as a modified Rankin Scale score (mRS) 0–2 at day 90 (right). Points/brackets indicate means and 95% confidence intervals.
Figure 2
Figure 2
Multivariable logistic regression analysis displaying the impact of age (x axis) according to the application of intravenous alteplase (IVT; blue/red) on functional outcome with 95% CIs including all patients. mRS, modified Rankin Scale.
Figure 3
Figure 3
Multivariable logistic regression analysis displaying the impact of IVT (intravenous thrombolysis; blue/red) and ASPECTS (Alberta Stroke Programme Early CT Score; x axis) on the probability of sICH (symptomatic intracranial hemorrhage; y axis) including all patients.
Figure 4
Figure 4
Bar graph showing the distribution of modified Rankin Scale (MRS) scores at 90 days according to the application of intravenous alteplase (IVT) and mechanical thrombectomy (MT). The upper bar graphs show outcome for patients with endovascular treatment (EVT) vs without treatment (BMT). The lower bar graphs show functional outcome for patients with successful MT after the first pass (mTICI 2b–3) for all direct MT patients, MT patients who received bridging IVT, BMT patients with and without IVT, respectively.

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