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      Intravenous Thrombolysis Is Not Associated with Increased Time to Endovascular Treatment

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          Abstract

          Background: Endovascular treatment (EVT) with or without intravenous thrombolysis (IVT) is effective and safe in is­chemic stroke caused by large vessel occlusion, but IVT might delay time to EVT or increase risk of intracranial hemorrhage (ICH). We assessed the influence of prior IVT on time to treatment and risk of ICH in patients treated with EVT. Methods: We analyzed data from the MR CLEAN Registry and included patients with an anterior circulation occlusion treated with EVT who presented directly to an intervention center, between 2014 and 2017. Primary endpoint was the door to groin time. Secondary outcomes were workflow time intervals and safety outcomes. We compared patients who received EVT only with patients who received IVT prior to EVT. Results: We included 1,427 patients directly referred to an intervention center of whom 1,023 (72%) received IVT + EVT. Adjusted door to CT imaging and door to groin time were shorter in IVT + EVT patients (difference 5.7 min [95% CI: 4.6–6.8] and 7.0 min [95% CI: 2.4–12], respectively) while CT imaging to groin time was similar between the groups. Early recanalization on digital subtraction angiography before EVT was seen more often after prior IVT (11 vs. 5.2%, aOR 2.4 [95% CI: 1.4–4.2]). Rates of symptomatic ICH were similar. Conclusion: Prior IVT did not delay door to groin times and was associated with higher rates of early recanalization, without increasing the risk of ICH. Our results do not warrant withholding IVT prior to EVT.

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          Most cited references13

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          The Heidelberg Bleeding Classification: Classification of Bleeding Events After Ischemic Stroke and Reperfusion Therapy.

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            Reducing in-hospital delay to 20 minutes in stroke thrombolysis.

            Efficacy of thrombolytic therapy for ischemic stroke decreases with time elapsed from symptom onset. We analyzed the effect of interventions aimed to reduce treatment delays in our single-center observational series. All consecutive ischemic stroke patients treated with IV alteplase (tissue plasminogen activator [tPA]) were prospectively registered in the Helsinki Stroke Thrombolysis Registry. A series of interventions to reduce treatment delays were implemented over the years 1998 to 2011. In-hospital delays were analyzed as annual median door-to-needle time (DNT) in minutes, with interquartile range. A total of 1,860 patients were treated between June 1995 and June 2011, which included 174 patients with basilar artery occlusion (BAO) treated mostly beyond 4.5 hours from symptom onset. In the non-BAO patients, the DNT was reduced annually, from median 105 minutes (65-120) in 1998, to 60 minutes (48-80) in 2003, further on to 20 minutes (14-32) in 2011. In 2011, we treated with tPA 31% of ischemic stroke patients admitted to our hospital. Of these, 94% were treated within 60 minutes from arrival. Performing angiography or perfusion imaging doubled the in-hospital delays. Patients with in-hospital stroke or arriving very soon from symptom onset had longer delays because there was no time to prepare for their arrival. With multiple concurrent strategies it is possible to cut the median in-hospital delay to 20 minutes. The key is to do as little as possible after the patient has arrived at the emergency room and as much as possible before that, while the patient is being transported.
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              Successful Reperfusion With Intravenous Thrombolysis Preceding Mechanical Thrombectomy in Large-Vessel Occlusions

              Background and Purpose Although current guidelines advocate pretreatment with intravenous thrombolysis (IVT) in all eligible acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) prior to mechanical thrombectomy (MT), there are observational data questioning the efficacy of this approach. One of the main arguments in favour of IVT pretreatment is the potential for tPA-induced successful reperfusion (SR) before the onset of endovascular procedure. Methods We performed a systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) and observational cohorts providing rates of SR with IVT in patients with LVO before the initiation of MT. We also performed subgroup analyses according to study type (RCTs vs. observational) and according to the inclusion per-protocol of patients with tandem (intracranial/extracranial) occlusions. Results We identified 13 eligible studies (7 RCTs & 6 observational cohorts), including 1561 AIS patients (median NIHSS score: 17) with LVO. SR following IVT and before MT was documented in 11% [95% confidence interval (95%CI): 7%–16%], with no difference among cohorts derived from RCTs and observational studies. There was significant heterogeneity across included studies both in the overall analysis and among subgroups (I 2 >84%, p for Cochran Q<0.001). Higher tPA-induced SR rates were documented in studies reporting the exclusion of tandem occlusions (17%, 95%CI:11%–23%) compared to the rest (7%, 95%CI: 4%–11%;p for subgroup differences: 0.003). Conclusions Pretreatment with systemic thrombolysis in LVO patients eligible for MT results in SR in one out of ten cases, negating the need for additional endovascular reperfusion. Tandem occlusions appear to be the least responsive to IVT pretreatment.
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                Author and article information

                Journal
                CED
                Cerebrovasc Dis
                10.1159/issn.1015-9770
                Cerebrovascular Diseases
                S. Karger AG
                1015-9770
                1421-9786
                2020
                July 2020
                02 July 2020
                : 49
                : 3
                : 321-327
                Affiliations
                [_a] aDepartment of Neurology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
                [_b] bDepartment of Radiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
                [_c] cDepartment of Radiology, St. Antonius Hospital, Nieuwegein, The Netherlands
                [_d] dDepartment of Neurology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands
                [_e] eDepartment of Neurology and Radiology, Haaglanden Medical Center, The Hague, The Netherlands
                [_f] fDepartment of Neurology, St. Antonius Hospital, Nieuwegein, The Netherlands
                Author notes
                *Wouter H. Hinsenveld, Department of Neurology, Maastricht University Medical Center, Postbus 5800, NL–6202 AZ Maastricht (The Netherlands), wouter.hinsenveld@mumc.nl
                Article
                508898 Cerebrovasc Dis 2020;49:321–327
                10.1159/000508898
                32615562
                f70912cd-89f8-4e7c-ba2c-cbc017446869
                © 2020 The Author(s) Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 02 March 2020
                : 24 May 2020
                Page count
                Figures: 2, Tables: 2, Pages: 7
                Categories
                Clinical Research in Stroke

                Geriatric medicine,Neurology,Cardiovascular Medicine,Neurosciences,Clinical Psychology & Psychiatry,Public health
                Acute stroke intervention,Endovascular treatment of acute stroke,Intravenous thrombolytic therapy of stroke,Workflow,Stroke organization

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