title: Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials.
abstract: BACKGROUND
  In 2015, five randomised trials showed efficacy of endovascular thrombectomy over standard medical care in patients with acute ischaemic stroke caused by occlusion of arteries of the proximal anterior circulation. In this meta-analysis we, the trial investigators, aimed to pool individual patient data from these trials to address remaining questions about whether the therapy is efficacious across the diverse populations included.
  
  
  METHODS
  We formed the HERMES collaboration to pool patient-level data from five trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA) done between December, 2010, and December, 2014. In these trials, patients with acute ischaemic stroke caused by occlusion of the proximal anterior artery circulation were randomly assigned to receive either endovascular thrombectomy within 12 h of symptom onset or standard care (control), with a primary outcome of reduced disability on the modified Rankin Scale (mRS) at 90 days. By direct access to the study databases, we extracted individual patient data that we used to assess the primary outcome of reduced disability on mRS at 90 days in the pooled population and examine heterogeneity of this treatment effect across prespecified subgroups. To account for between-trial variance we used mixed-effects modelling with random effects for parameters of interest. We then used mixed-effects ordinal logistic regression models to calculate common odds ratios (cOR) for the primary outcome in the whole population (shift analysis) and in subgroups after adjustment for age, sex, baseline stroke severity (National Institutes of Health Stroke Scale score), site of occlusion (internal carotid artery vs M1 segment of middle cerebral artery vs M2 segment of middle cerebral artery), intravenous alteplase (yes vs no), baseline Alberta Stroke Program Early CT score, and time from stroke onset to randomisation.
  
  
  RESULTS
  We analysed individual data for 1287 patients (634 assigned to endovascular thrombectomy, 653 assigned to control). Endovascular thrombectomy led to significantly reduced disability at 90 days compared with control (adjusted cOR 2.49, 95% CI 1.76-3.53; p<0.0001). The number needed to treat with endovascular thrombectomy to reduce disability by at least one level on mRS for one patient was 2.6. Subgroup analysis of the primary endpoint showed no heterogeneity of treatment effect across prespecified subgroups for reduced disability (pinteraction=0.43). Effect sizes favouring endovascular thrombectomy over control were present in several strata of special interest, including in patients aged 80 years or older (cOR 3.68, 95% CI 1.95-6.92), those randomised more than 300 min after symptom onset (1.76, 1.05-2.97), and those not eligible for intravenous alteplase (2.43, 1.30-4.55). Mortality at 90 days and risk of parenchymal haematoma and symptomatic intracranial haemorrhage did not differ between populations.
  
  
  CONCLUSIONS
  Endovascular thrombectomy is of benefit to most patients with acute ischaemic stroke caused by occlusion of the proximal anterior circulation, irrespective of patient characteristics or geographical location. These findings will have global implications on structuring systems of care to provide timely treatment to patients with acute ischaemic stroke due to large vessel occlusion.
  
  
  BACKGROUND
  Medtronic.
authors.affiliation: Departments of Clinical Neuroscience and Radiology, Hotchkiss Brain Institute, Cummings School of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Mayank
authors.initials: M
authors.lastname: Goyal
authors.affiliation: Departments of Clinical Neuroscience and Radiology, Hotchkiss Brain Institute, Cummings School of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Bijoy K
authors.initials: BK
authors.lastname: Menon
authors.affiliation: Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, Netherlands.
authors.forename: Wim H
authors.initials: WH
authors.lastname: van Zwam
authors.affiliation: Erasmus MC University Medical Center, Rotterdam, Netherlands.
authors.forename: Diederik W J
authors.initials: DW
authors.lastname: Dippel
authors.affiliation: Department of Radiology, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Mitchell
authors.affiliation: Departments of Clinical Neuroscience and Radiology, Hotchkiss Brain Institute, Cummings School of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Demchuk
authors.affiliation: Hospital Germans Trias y Pujol, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Dávalos
authors.affiliation: Academic Medical Center, Amsterdam, Netherlands.
authors.forename: Charles B L M
authors.initials: CB
authors.lastname: Majoie
authors.affiliation: Erasmus MC University Medical Center, Rotterdam, Netherlands.
authors.forename: Aad
authors.initials: A
authors.lastname: van der Lugt
authors.affiliation: Hospital de Bellvitge, Barcelona, Spain.
authors.forename: Maria A
authors.initials: MA
authors.lastname: de Miquel
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Donnan
authors.affiliation: Academic Medical Center, Amsterdam, Netherlands.
authors.forename: Yvo B W E M
authors.initials: YB
authors.lastname: Roos
authors.affiliation: Hospital Guy de Chaulliac, Montpellier, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Bonafe
authors.affiliation: UCLA Medical Center, Los Angeles, CA, USA.
authors.forename: Reza
authors.initials: R
authors.lastname: Jahan
authors.affiliation: Department of Neurology, University Hospital Essen, Essen, Germany.
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Diener
authors.affiliation: Academic Medical Center, Amsterdam, Netherlands.
authors.forename: Lucie A
authors.initials: LA
authors.lastname: van den Berg
authors.affiliation: State University of New York, Buffalo, Buffalo, NY, USA.
authors.forename: Elad I
authors.initials: EI
authors.lastname: Levy
authors.affiliation: Academic Medical Center, Amsterdam, Netherlands.
authors.forename: Olvert A
authors.initials: OA
authors.lastname: Berkhemer
authors.affiliation: University of Toronto, Toronto, ON, Canada.
authors.forename: Vitor M
authors.initials: VM
authors.lastname: Pereira
authors.affiliation: University of Edmonton, Edmonton, AB, Canada.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Rempel
authors.affiliation: Hospital Germans Trials y Pujol, Barcelona, Spain.
authors.forename: Mònica
authors.initials: M
authors.lastname: Millán
authors.affiliation: Department of Medicine and Neurology, Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Davis
authors.affiliation: CHUM Notre-Dame Hospital, Montreal, QC, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Roy
authors.affiliation: Beaumont Hospital, Dublin, Ireland.
authors.forename: John
authors.initials: J
authors.lastname: Thornton
authors.affiliation: Hospital Clinic, Barcelona, Spain.
authors.forename: Luis San
authors.initials: LS
authors.lastname: Román
authors.affiliation: Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Ribó
authors.affiliation: Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, Netherlands.
authors.forename: Debbie
authors.initials: D
authors.lastname: Beumer
authors.affiliation: Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Stouch
authors.affiliation: Altair Biostatistics, St Louis Park, MN, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Brown
authors.affiliation: Department of Medicine and Neurology, Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Bruce C V
authors.initials: BC
authors.lastname: Campbell
authors.affiliation: Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, Netherlands.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: van Oostenbrugge
authors.affiliation: David Geffen School of Medicine, University of Los Angeles, Los Angeles, CA, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Saver
authors.affiliation: Departments of Clinical Neuroscience and Radiology, Hotchkiss Brain Institute, Cummings School of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hill
authors.affiliation: University of Pittsburgh Medical Center Stroke Institute, Presbyterian University Hospital, Pittsburgh, PA, USA. Electronic address: jovintg@upmc.edu.
authors.forename: Tudor G
authors.initials: TG
authors.lastname: Jovin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000150:complications / Q000628:therapy*; D057510:Endovascular Procedures / Q000379:methods*; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D020300:Intracranial Hemorrhages / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000209:etiology / Q000628:therapy*; D017131:Thrombectomy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator