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Original research
Clinical outcome of patients with mild pre-stroke morbidity following endovascular treatment: a HERMES substudy
  1. Rosalie V McDonough1,2,
  2. Johanna M Ospel3,
  3. Charles B L M Majoie4,
  4. Jeffrey L Saver5,
  5. Philip White6,
  6. Diederik W J Dippel7,
  7. Scott B Brown8,
  8. Andrew M Demchuk9,
  9. Tudor G Jovin10,
  10. Peter J Mitchell11,
  11. Serge Bracard12,
  12. Bruce C V Campbell13,14,
  13. Keith W Muir15,
  14. Michael D Hill9,
  15. Francis Guillemin16,
  16. Mayank Goyal2
  17. on behalf of the HERMES collaborators
    1. 1Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg Eppendorf, Hamburg, Germany
    2. 2Radiology, University of Calgary, Calgary, Alberta, Canada
    3. 3Neuroradiology, University Hospital Basel, Basel, Switzerland
    4. 4Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
    5. 5Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
    6. 6Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
    7. 7Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands
    8. 8BRIGHT Research Partners, Mooresville, North Carolina, USA
    9. 9Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada
    10. 10Neurology, Cooper University Hospital, Camden, New Jersey, USA
    11. 11Radiology, The Royal Melbourne Hospital, Parkville, Victoria, Australia
    12. 12Neuroradiology, Université de Lorraine, Nancy, France
    13. 13Medicine, University of Melbourne, Parkville, Victoria, Australia
    14. 14Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
    15. 15Institute of Neuroscience and Psychology, Queen Elizabeth University Hospital, Glasgow, UK
    16. 16Department of Clinical Epidemiology, University Hospital Centre Nancy, Nancy, France
    1. Correspondence to Dr Mayank Goyal, Diagnostic Imaging, University of Calgary, Calgary, AB T2N 1N4, Canada; mgoyal2412{at}gmail.com

    Abstract

    Background Analyses of the effect of pre-stroke functional levels on the outcome of endovascular therapy (EVT) have focused on the course of patients with moderate to substantial pre-stroke disability. The effect of complete freedom from pre-existing disability (modified Rankin Scale (mRS) 0) versus predominantly mild pre-existing disability/symptoms (mRS 1–2) has not been well delineated.

    Methods The HERMES meta-analysis pooled data from seven randomized trials that tested the efficacy of EVT. We tested for a multiplicative interaction effect of pre-stroke mRS on the relationship between treatment and outcomes. Ordinal regression was used to assess the association between EVT and 90-day mRS (primary outcome) in the subgroup of patients with pre-stroke mRS 1–2. Multivariable regression modeling was then used to test the effect of mild pre-stroke disability/symptoms on the primary and secondary outcomes (delta-mRS, mRS 0–2/5–6) compared with patients with pre-stroke mRS 0.

    Results We included 1764 patients, of whom 199 (11.3%) had pre-stroke mRS 1–2. No interaction effect of pre-stroke mRS on the relationship between treatment and outcome was observed. Patients with pre-stroke mRS 1–2 had worse outcomes than those with pre-stroke mRS 0 (adjusted common OR (acOR) 0.53, 95% CI 0.40 to 0.70). Nonetheless, a significant benefit of EVT was observed within the mRS 1–2 subgroup (cOR 2.08, 95% CI 1.22 to 3.55).

    Conclusions Patients asymptomatic/without disability prior to onset have better outcomes following EVT than patients with mild disability/symptoms. Patients with pre-stroke mRS 1–2, however, more often achieve good outcomes with EVT compared with conservative management. These findings indicate that mild pre-existing disability/symptoms influence patient prognosis after EVT but do not diminish the EVT treatment effect.

    • stroke
    • thrombectomy

    Data availability statement

    Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplemental information. Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Raw data will be made available by the corresponding author upon reasonable request after approval by the HERMES Executive Committee.

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    Data availability statement

    Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplemental information. Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Raw data will be made available by the corresponding author upon reasonable request after approval by the HERMES Executive Committee.

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    Footnotes

    • Twitter @johanna_ospel, @mihill68

    • RVM and JMO contributed equally.

    • Collaborators The HERMES collaborators: Olvert A Berkhemer; Puck SS Fransen; Debbie Beumer; Lucie A van den Berg; Hester F Lingsma; Albert J Yoo; Wouter J Schonewille; Jan Albert Vos; Paul J Nederkoorn; Marieke JH Wermer; Marianne AA van Walderveen; Julie Staals; Jeannette Hofmeijer; Jacques A van Oostayen; Geert J Lycklama à Nijeholt; Jelis Boiten; Patrick A Brouwer; Bart J Emmer; Sebastiaan F de Bruijn; Lukas C van Dijk; Jaap Kappelle; Rob H Lo; Ewoud J vanDijk; Joost de Vries; Paul LM de Kort; Willem Jan J van Rooij; Jan SP van den Berg; Boudewijn AAM vanHasselt; Leo AM Aerden; René J Dallinga; Marieke C Visser; Joseph CJ Bot; Patrick C Vroomen; Omid Eshghi; Tobien HCML Schreuder; Roel JJ Heijboer; Koos Keizer; Alexander V Tielbeek; Heleen M denHertog; Dick G Gerrits; Renske M vandenBerg-Vos; Giorgos B Karas; Ewout W Steyerberg; Zwenneke Flach; Henk A Marquering; Marieke ES Sprengers; Sjoerd FM Jenniskens; Ludo FM Beenen; René vandenBerg; Peter J Koudstaal; Wim H vanZwam; Yvo BWEM Roos; Aad vander Lugt; Robert J vanOostenbrugge; Charles BLM Majoie; Diederik WJ Dippel; Martin M Brown; Thomas Liebig; Theo Stijnen; Tommy Andersson; Heinrich Mattle; Nils Wahlgren; Esther van der Heijden; Naziha Ghannouti; Nadine Fleitour; Imke Hooijenga; Corina Puppels; Wilma Pellikaan; Annet Geerling; Annemieke Lindl-Velema; Gina van Vemde; Ans de Ridder; Paut Greebe; José de Bont-Stikkelbroeck; Joke de Meris; Kirsten Janssen; Willy Struijk; Silvan Licher; Nikki Boodt; Adriaan Ros; Esmee Venema; Ilse Slokkers; Raymie-Jayce Ganpat; Maxim Mulder; Nawid Saiedie; Alis Heshmatollah; Stefanie Schipperen; Stefan Vinken; Tiemen van Boxtel; Jeroen Koets; Merel Boers; Emilie Santos; Jordi Borst; Ivo Jansen; Manon Kappelhof; Marit Lucas; Ralph Geuskens; Renan Sales Barros; Roeland Dobbe; Marloes Csizmadia; MD Hill; M Goyal; AM Demchuk; BK Menon; M Eesa; KJ Ryckborst; MR Wright; NR Kamal; L Andersen; PA Randhawa; T Stewart; S Patil; P Minhas; M Almekhlafi; S Mishra; F Clement; T Sajobi; A Shuaib; WJ Montanera; D Roy; FL Silver; TG Jovin; DF Frei; B Sapkota; JL Rempel; J Thornton; D Williams; D Tampieri; AY Poppe; D Dowlatshahi; JH Wong; AP Mitha; S Subramaniam; G Hull; MW Lowerison; T Sajobi; M Salluzzi; MR Wright; M Maxwell; S Lacusta; E Drupals; K Armitage; PA Barber; EE Smith; WF Morrish; SB Coutts; C Derdeyn; B Demaerschalk; D Yavagal; R Martin; R Brant; Y Yu; RA Willinsky; WJ Montanera; A Weill; C Kenney; H Aram; T Stewart; PK Stys; TW Watson; G Klein; D Pearson; P Couillard; A Trivedi; D Singh; E Klourfeld; O Imoukhuede; D Nikneshan; S Blayney; R Reddy; P Choi; M Horton; T Musuka; V Dubuc; TS Field; J Desai; S Adatia; A Alseraya; V Nambiar; R van Dijk; JH Wong; AP Mitha; WF Morrish; M Eesa; NJ Newcommon; A Shuaib; B Schwindt; KS Butcher; T Jeerakathil; B Buck; K Khan; SS Naik; DJ Emery; RJ Owen; TB Kotylak; RA Ashforth; TA Yeo; D McNally; M Siddiqui; M Saqqur; D Hussain; H Kalashyan; A Manosalva; M Kate; L Gioia; S Hasan; A Mohammad; M Muratoglu; D Williams; J Thornton; A Cullen; P Brennan; A O’Hare; S Looby; D Hyland; S Duff; M McCusker; B Hallinan; S Lee; J McCormack; A Moore; M O'Connor; C Donegan; LBrewer; A Martin; S Murphy; K O'Rourke; S Smyth; P Kelly; T Lynch; T Daly; P O'Brien; A O'Driscoll; M Martin; T Daly; R Collins; T Coughlan; D McCabe; S Murphy; D O'Neill; M Mulroy; O Lynch; T Walsh; M O’Donnell; T Galvin; J Harbison; P McElwaine; K Mulpeter; C McLoughlin; M Reardon; E Harkin; E Dolan; M Watts; N Cunningham; C Fallon; S Gallagher; P Cotter; M Crowe; R Doyle; I Noone; M Lapierre; VA Coté; S Lanthier; C Odier; A Durocher; J Raymond; A Weill; N Daneault; Y Deschaintre; B Jankowitz; L Baxendell; L Massaro; C Jackson-Graves; S Decesare; P Porter; K Armbruster; A Adams; J Billigan; J Oakley; A Ducruet; A Jadhav; D-V Giurgiutiu; A Aghaebrahim; V Reddy; M Hammer; M Starr; V Totoraitis; L Wechsler; S Streib; S Rangaraju; D Campbell; M Rocha; D Gulati; FL Silver; T Krings; L Kalman; A Cayley; J Williams; T Stewart; R Wiegner; LK Casaubon; C Jaigobin; JM del Campo; E Elamin; 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Pauline Renou; Olivier Fleury; Anne Pasco-Papon; Frédéric Dubas; Jildaz Caroff; Sophie Godard Ducceschi; Marie-Aurélie Hamon; Alderic Lecluse; Guillaume Marc; Maurice Giroud; Frédéric Ricolfi; Yannick Bejot; Adrien Chavent; Arnaud Gentil; Apolline Kazemi; Guy-Victor Osseby; Charlotte Voguet; Marie-Hélène Mahagne; Jacques Sedat; Yves Chau; Laurent Suissa; Sylvain Lachaud; Emmanuel Houdart; Christian Stapf; Frédérique Buffon Porcher; Hugues Chabriat; Pierre Guedin; Dominique Herve; Eric Jouvent; Jérôme Mawet; Jean-Pierre Saint-Maurice; Hans-Martin Schneble; Francis Turjman; Norbert Nighoghossian; Nadia-Nawel Berhoune; Françoise Bouhour; Tae-Hee Cho; Laurent Derex; Sandra Felix; Hélène Gervais-Bernard; Benjamin Gory; Luis Manera; Laura Mechtouff; Thomas Ritzenthaler; Roberto Riva; Fabrizio Salaris Silvio; Caroline Tilikete; Raphael Blanc; Michaël Obadia; Mario Bruno Bartolini; Antoine Gueguen; Michel Piotin; Silvia Pistocchi; Hocine Redjem; Jacques Drouineau; Jean-Philippe Neau; Gaelle Godeneche; Matthias Lamy; Emilia Marsac; Stephane Velasco; Pierre Clavelou; Emmanuel Chabert; Nathalie Bourgois; Catherine Cornut-Chauvinc; Anna Ferrier; Jean Gabrillargues; Betty Jean; Anna-Raquel Marques; Nicolas Vitello; Olivier Detante; Marianne Barbieux; Kamel Boubagra; Isabelle Favre Wiki; Katia Garambois; Florence Tahon; Vasdev Ashok; Charlotte Voguet; Oguzhan Coskun; Pierre Guedin; Georges Rodesch; Bertrand Lapergue; Frédéric Bourdain; Serge Evrard; Philippe Graveleau; Jean Pierre Decroix; Adrien Wang; François Sellal; Guido Ahle; Gabriela Carelli; Marie-Hélène Dugay; Claude Gaultier; Ariel Pablo Lebedinsky; Lavinia Lita; Raul Mariano Musacchio; Catherine Renglewicz-Destuynder; Alain Tournade; Françis Vuillemet; Francisco Macian Montoro; Charbel Mounayer; Frederic Faugeras; Laetitia Gimenez; Catherine Labach; Géraldine Lautrette; Christian Denier; Guillaume Saliou; Olivier Chassin; Claire Dussaule; Elsa Melki; Augustin Ozanne; Francesco Puccinelli; Marina Sachet; Mariana Sarov; Jean-François Bonneville; Thierry Moulin; Alessandra Biondi; Elisabeth De Bustos Medeiros; Fabrice Vuillier; Patrick Courtheoux; Fausto Viader; Marion Apoil-Brissard; Mathieu Bataille; Anne-Laure Bonnet; Julien Cogez; Apolline Kazemi; Emmanuel Touze; Xavier Leclerc; Didier Leys; Mohamed Aggour; Pierre Aguettaz; Marie Bodenant; Charlotte Cordonnier; Dominique Deplanque; Marie Girot; Hilde Henon; Erwah Kalsoum; Christian Lucas; Jean-Pierre Pruvo; Paolo Zuniga; Alain Bonafé; Caroline Arquizan; Vincent Costalat; Paolo Machi; Isabelle Mourand; Carlos Riquelme; Pierre Bounolleau; Charles Arteaga; Anthony Faivre; Marc Bintner; Patrice Tournebize; Cyril Charlin; Françoise Darcel; Pascale Gauthier-Lasalarie; Marcia Jeremenko; Servane Mouton; Jean-Baptiste Zerlauth; Chantal Lamy; Deramond Hervé; Hosseini Hassan; André Gaston; Francis-Guy Barral; Pierre Garnier; Rémy Beaujeux; Valérie Wolff; Denis Herbreteau; Séverine Debiais; Alicia Murray; Gary Ford; Keith W Muir; Philip White; Martin M Brown; Andy Clifton; Janet Freeman; Ian Ford; Hugh Markus; Joanna Wardlaw; Kennedy R Lees; Andy Molyneux; Thompson Robinson; Steff Lewis; John Norrie; Fergus Robertson; Richard Perry; Anand Dixit; Geoffrey Cloud; Andrew Clifton; Jeremy Madigan; Christine Roffe; Sanjeev Nayak; Kyriakos Lobotesis; Craig Smith; Amit Herwadkar; Naga Kandasamy; Tony Goddard; John Bamford; Ganesh Subramanian; Rob Lenthall; Edward Littleton; Sal Lamin; Kelley Storey; Rita Ghatala; Azra Banaras; John Aeron-Thomas; Bath Hazel; Holly Maguire; Emelda Veraque; Louise Harrison; Rekha Keshvara; James Cunningham.

    • Contributors MG: conceptualization, drafting, and critical revision and final approval of the manuscript (guarantor). RVM, JMO: data acquisition, drafting, and critical revision and final approval of the manuscript. SB: statistical analysis and critical revision and final approval of the manuscript. Remaining authors: data curation, critical revision and final approval of the manuscript.

    • Funding The HERMES collaboration is supported by an unrestricted grant from Medtronic to the University of Calgary. The company was not involved in the design, analysis, or writing of this study.

    • Competing interests No authors received any payments for work on the submitted manuscript. RVM reports no conflicts. JMO reports support from the University of Basel Research Foundation, Julia Bangerter Rhyner Foundation, and Freiwillige AkademischeGesellschaft Basel. JLS reports being an employee of the University of California; serving as an unpaid site investigator in multicenter trials run by Medtronic and Stryker for which the University of California Regents received payments on the basis of clinical trial contracts for the number of subjects enrolled; receiving funding for services as a scientific consultant regarding trial design and conduct to Medtronic, Stryker, Cerenovus and Rapid Medical. The UC Regents have patent rights in endovascular retrievers. DWJD reports that his institution has received honoraria for his speaking from Stryker and grant funding from the Dutch Heart Foundation, AngioCare BV, Medtronic/EV3, MEDAC GmbH/LAMEPRO, Penumbra, Stryker, and Top Medical/ Concentric. CBLMM reports grants paid to the institution from the Netherlands Cardiovascular Research Committee (CVON)/Dutch Heart Foundation, the European Commission, Stichting Toegepast Wetenschappelijk Instituut voor Neuromodulatie (TWIN) foundation and Stryker. He is shareholder of Nicolab, a company that focuses on the use of artificial intelligence for medical image analysis. TGJ reports receiving grants from Stryker Neurovascular and consultant fees for Anaconda, VizAI, FreeOx Biotech, Corindus, Cerenovus, Route92, Blockade Medical and Medtronic. SB reports grants from the French Ministry of Health during the conduct of the THRACE study (Trial and Cost Effectiveness Evaluation of Intraarterial Thrombectomy in Acute Ischemic Stroke) and personal fees from General Electric Medical Systems and non-financial support from Microvention Europe outside the submitted work. FG reports grants from the French Ministry of Health during the conduct of the THRACE study. BCVC reports that his institution received a grant to support the EXTEND-IA trial (Extending the Time for Thrombolysis in Emergency Neurological Deficits - Intra-Arterial) from Covidien/Medtronic. He reports grant funding from the National Health and Medical Research Council of Australia and Medtronic and fellowships from the National Heart Foundation of Australia, National Stroke Foundation of Australia, and Royal Australasian College of Physicians. PJM reports that his institution received grants from Medtronic and Stryker; he received consultant fees from Stryker and Microvention. PW reports grants from UK National Institutes for Health Research, Microvention Terumo, Stryker, Medtronic, and Penumbra; he received consultation fees from Microvention Terumo and is an Editorial Board member of JNIS. KWM has received consultant fees from Boehringer Ingelheim, Bayer and Daiichi-Sankyo. SBB reports receiving consulting fees from Medtronic/Covidien and personal fees from the University of Calgary. AMD reports receiving grant support and personal fees from Medtronic and has a patent with Circle Cardiovascular Imaging on stroke imaging software. MDH reports unrestricted grant funding for the ESCAPE trial to University of Calgary from Covidien/Medtronic and active/in-kind support consortium of public/charitable sources (Heart and Stroke Foundation, Alberta Innovates Health Solutions, Alberta Health Services) and the University of Calgary (Hotchkiss Brain Institute, Departments of Clinical Neurosciences and Radiology, and Calgary Stroke Program); grant funding from Boehringer Ingelheim, NoNo, Inc, and Stryker; personal fees from Merck, non-financial support from Hoffmann-La Roche Canada. In addition, MDH has a submitted patent for triaging systems in ischemic stroke and owns stock in Calgary Scientific, a company that focuses on medical imaging software. MG reports receiving an unrestricted institutional grant from Medtronic; he received a grant from Stryker and consulting fees from Stryker, Microvention, Mentice; and he holds patent rights in systems and methods for acute stroke diagnosis with GE Healthcare.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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