• Wouter van der Steen, Rob A van de Graaf, Vicky Chalos, Hester F Lingsma, van DoormaalPieter JanPJDepartment of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, Netherlands., Jonathan M Coutinho, Bart J Emmer, Inger de Ridder, Wim van Zwam, H Bart van der Worp, Irene van der Schaaf, GonsRob A RRARDepartment of Neurology, Catharina Hospital, Eindhoven, Netherlands., Lonneke S F Yo, Jelis Boiten, Ido van den Wijngaard, Jeannette Hofmeijer, Jasper Martens, Wouter Schonewille, Jan Albert Vos, Anil Man Tuladhar, Karlijn F de Laat, Boudewijn van Hasselt, Michel Remmers, Douwe Vos, Anouk Rozeman, Otto Elgersma, Maarten Uyttenboogaart, BokkersReinoud P HRPHDepartment of Radiology, Medical Imaging Center, University Medical Center Groningen, Groningen, Netherlands., Julia van Tuijl, Issam Boukrab, René van den Berg, BeenenLudo F MLFMDepartment of Radiology & Nuclear Medicine, Amsterdam University Medical Centers, location AMC, Amsterdam, Netherlands., Stefan D Roosendaal, Alida Annechien Postma, Menno Krietemeijer, Geert Lycklama, Frederick J A Meijer, Sebastiaan Hammer, Anouk van der Hoorn, Albert J Yoo, Dick Gerrits, TruijmanMartine T BMTBDepartment of Neurology, Erasmus MC University Medical Center, Rotterdam, Netherlands., Sanne Zinkstok, Peter J Koudstaal, Sanne Manschot, Henk Kerkhoff, Daan Nieboer, Olvert Berkhemer, Lennard Wolff, P Matthijs van der Sluijs, Henk van Voorst, Manon Tolhuisen, RoosYvo B W E MYBWEMDepartment of Neurology, Amsterdam University Medical Centers, location AMC, Amsterdam, Netherlands., MajoieCharles B L MCBLMDepartment of Radiology & Nuclear Medicine, Amsterdam University Medical Centers, location AMC, Amsterdam, Netherlands., Julie Staals, Robert J van Oostenbrugge, JenniskensSjoerd F MSFMDepartment of Medical Imaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands., Lukas C van Dijk, Heleen M den Hertog, Adriaan C G M van Es, Aad van der Lugt, DippelDiederik W JDWJDepartment of Neurology, Erasmus MC University Medical Center, Rotterdam, Netherlands., Bob Roozenbeek, and MR CLEAN-MED investigators.
• Department of Neurology, Erasmus MC University Medical Center, Rotterdam, Netherlands; Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, Netherlands. Electronic address: w.vandersteen@erasmusmc.nl.
• Lancet. 2022 Mar 12; 399 (10329): 1059-1069.

BackgroundAspirin and unfractionated heparin are often used during endovascular stroke treatment to improve reperfusion and outcomes. However, the effects and risks of anti-thrombotics for this indication are unknown. We therefore aimed to assess the safety and efficacy of intravenous aspirin, unfractionated heparin, both, or neither started during endovascular treatment in patients with ischaemic stroke.MethodsWe did an open-label, multicentre, randomised controlled trial with a 2 × 3 factorial design in 15 centres in the Netherlands. We enrolled adult patients (ie, ≥18 years) with ischaemic stroke due to an intracranial large-vessel occlusion in the anterior circulation in whom endovascular treatment could be initiated within 6 h of symptom onset. Eligible patients had a score of 2 or more on the National Institutes of Health Stroke Scale, and a CT or MRI ruling out intracranial haemorrhage. Randomisation was done using a web-based procedure with permuted blocks and stratified by centre. Patients were randomly assigned (1:1) to receive either periprocedural intravenous aspirin (300 mg bolus) or no aspirin, and randomly assigned (1:1:1) to receive moderate-dose unfractionated heparin (5000 IU bolus followed by 1250 IU/h for 6 h), low-dose unfractionated heparin (5000 IU bolus followed by 500 IU/h for 6 h), or no unfractionated heparin. The primary outcome was the score on the modified Rankin Scale at 90 days. Symptomatic intracranial haemorrhage was the main safety outcome. Analyses were based on intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. This trial is registered with the International Standard Randomised Controlled Trial Number, ISRCTN76741621.FindingsBetween Jan 22, 2018, and Jan 27, 2021, we randomly assigned 663 patients; of whom, 628 (95%) provided deferred consent or died before consent could be asked and were included in the modified intention-to-treat population. On Feb 4, 2021, after unblinding and analysis of the data, the trial steering committee permanently stopped patient recruitment and the trial was stopped for safety concerns. The risk of symptomatic intracranial haemorrhage was higher in patients allocated to receive aspirin than in those not receiving aspirin (43 [14%] of 310 vs 23 [7%] of 318; adjusted OR 1·95 [95% CI 1·13-3·35]) as well as in patients allocated to receive unfractionated heparin than in those not receiving unfractionated heparin (44 [13%] of 332 vs 22 [7%] of 296; 1·98 [1·14-3·46]). Both aspirin (adjusted common OR 0·91 [95% CI 0·69-1·21]) and unfractionated heparin (0·81 [0·61-1·08]) led to a non-significant shift towards worse modified Rankin Scale scores.InterpretationPeriprocedural intravenous aspirin and unfractionated heparin during endovascular stroke treatment are both associated with an increased risk of symptomatic intracranial haemorrhage without evidence for a beneficial effect on functional outcome.FundingThe Collaboration for New Treatments of Acute Stroke consortium, the Brain Foundation Netherlands, the Ministry of Economic Affairs, Stryker, Medtronic, Cerenovus, and the Dutch Heart Foundation.Copyright © 2022 Elsevier Ltd. All rights reserved.

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