Background: Evidence regarding whether imaging can be used effectively to select patients for endovascular thrombectomy (EVT) is scarce. We aimed to investigate the association between baseline imaging features and safety and efficacy of EVT in acute ischaemic stroke caused by anterior large-vessel occlusion. Methods: In this meta-analysis of individual patient-level data, the HERMES collaboration identified in PubMed seven randomised trials in endovascular stroke that compared EVT with standard medical therapy, published between Jan 1, 2010, and Oct 31, 2017. Only trials that required vessel imaging to identify patients with proximal anterior circulation ischaemic stroke and that used predominantly stent retrievers or second-generation neurothrombectomy devices in the EVT group were included. Risk of bias was assessed with the Cochrane handbook methodology. Central investigators, masked to clinical information other than stroke side, categorised baseline imaging features of ischaemic change with the Alberta Stroke Program Early CT Score (ASPECTS) or according to involvement of more than 33% of middle cerebral artery territory, and by thrombus volume, hyperdensity, and collateral status. The primary endpoint was neurological functional disability scored on the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included symptomatic intracranial haemorrhage, parenchymal haematoma type 2 within 5 days of randomisation, and mortality within 90 days. For the primary analysis, we used mixed-methods ordinal logistic regression adjusted for age, sex, National Institutes of Health Stroke Scale score at admission, intravenous alteplase, and time from onset to randomisation, and we used interaction terms to test whether imaging categorisation at baseline modifies the association between treatment and outcome. This meta-analysis was prospectively designed by the HERMES executive committee but has not been registered. Findings: Among 1764 pooled patients, 871 were allocated to the EVT group and 893 to the control group. Risk of bias was low except in the THRACE study, which used unblinded assessment of outcomes 90 days after randomisation and MRI predominantly as the primary baseline imaging tool. The overall treatment effect favoured EVT (adjusted common odds ratio [cOR] for a shift towards better outcome on the mRS 2·00, 95% CI 1·69–2·38; p<0·0001). EVT achieved better outcomes at 90 days than standard medical therapy alone across a broad range of baseline imaging categories. Mortality at 90 days (14·7% vs 17·3%, p=0·15), symptomatic intracranial haemorrhage (3·8% vs 3·5%, p=0·90), and parenchymal haematoma type 2 (5·6% vs 4·8%, p=0·52) did not differ between the EVT and control groups. No treatment effect modification by baseline imaging features was noted for mortality at 90 days and parenchymal haematoma type 2. Among patients with ASPECTS 0–4, symptomatic intracranial haemorrhage was seen in ten (19%) of 52 patients in the EVT group versus three (5%) of 66 patients in the control group (adjusted cOR 3·94, 95% CI 0·94–16·49; pinteraction=0·025), and among patients with more than 33% involvement of middle cerebral artery territory, symptomatic intracranial haemorrhage was observed in 15 (14%) of 108 patients in the EVT group versus four (4%) of 113 patients in the control group (4·17, 1·30–13·44, pinteraction=0·012). Interpretation: EVT achieves better outcomes at 90 days than standard medical therapy across a broad range of baseline imaging categories, including infarcts affecting more than 33% of middle cerebral artery territory or ASPECTS less than 6, although in these patients the risk of symptomatic intracranial haemorrhage was higher in the EVT group than the control group. This analysis provides preliminary evidence for potential use of EVT in patients with large infarcts at baseline. Funding: Medtronic.
Bibliographical noteFunding Information:
BKM has a patent pending related to methods of triaging patients with acute stroke. AD reports grants from Medtronic. CBLMM reports grants from CVON/Dutch Heart Foundation, the European Commission, the TWIN Foundation, and Stryker (all paid to institution), and owns stock in Nico.lab, a company that focuses on the use of artificial intelligence for medical image analysis. BCVC reports grants from the Australian National Health and Medical Research Council, Royal Australasian College of Physicians, Royal Melbourne Hospital Foundation, National Heart Foundation of Australia, National Stroke Foundation of Australia, and Covidien (Medtronic). JLS reports serving as an unpaid site investigator in multicentre trials sponsored by Covidien, Medtronic/Abbott, Stryker, and Neuravi/Abbott, for which the University of California, Los Angeles, received payments on the basis of clinical trial contracts for the number of participants enrolled; receiving contracted hourly payments and travel reimbursement from Covidien, Medtronic/Abbott, Stryker, and Neuravi/Abbott; and receiving stock options from Rapid Medical for service on trial steering committees and advising on rigorous trial design and conduct. The University of California, Los Angeles, has patent rights in retrieval devices for stroke. HM is founder of and holds shares in Nico.lab. GR reports personal fees from Bayer, Boehringer Ingelheim, Pfizer, and Daiichi Sankyo. DWJD reports grants from the Dutch Heart Foundation, AngioCare BV, Medtronic/Covidien/EV3, MEDAC GmbH/LAMEPRO, Penumbra Inc, and Stryker during the conduct of the MR CLEAN study. DY reports personal fees, non-financial support, travel support, and moderate support from Medtronic, and is on the steering committee of SWIFT PRIME, personal fees from Neural Analytics, and personal fees, moderate support, and travel support for the Clot Summit from Cerenovus. SMD reports personal fees as an advisory board member and travel support from Boehringer Ingelheim and personal fees from Medtronic. GAD reports grants from the Australian National Health and Medical Research Council, and is on the advisory panels of AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharpe Dohme, Pfizer, and Servier. AvdL reports grants from the Dutch Heart Foundation, Stryker, Penumbra Inc, and Medtronic outside the submitted work, and reports unrestricted grants from AngioCare BV, Covidien/EV3, MEDAC GmbH/LAMEPRO, Stryker, and Penumbra Inc. AMD reports personal fees from Medtronic. Academic Medical Center (Amsterdam, Netherlands) received funds from Stryker for consultations by OAB. AMMB owns stock in Nico.lab. GAF reports personal fees from Stryker, Pfizer, Bayer, AstraZeneca, and Cerevast, and grants and personal fees from Medtronic. KWM reports grants from Medtronic and Codman. SB reports personal fees from Medtronic. TJ owns stock in and is an adviser for Anaconda, Silk Road, Route 92, Blockade Medical, FreeOx Biotech, non-financial support from Stryker Neurovascular, and personal fees from Cerenovus. WHvZ reports personal fees from Modest and Stryker. PJM reports non-financial support from Johnson & Johnson, and grants from Stryker and Medtronic. MDH reports grants from Medtronic; personal fees from Merck; non-financial support from Hoffmann-La Roche Canada, grants from Covidien (Medtronic), Boehringer Ingleheim, and Stryker. Additionally, MDH has a patent pending (US Patent Office number 62/086,077), owns stock in Calgary Scientific, a company that focuses on medical imaging software, is a director of the Canadian Federation of Neurological Sciences, a not-for-profit group, and has received grant support from Alberta Innovates Health Solutions, Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and US National Institutes of Neurological Disorders and Stroke. PW reports grants and personal fees from MicroVention Terumo, and personal fees from Stryker and Codman. MG reports grants from Medtronic and personal fees from Stryker, Medtronic, MicroVention, and Cerenovus, and grants from Stryker. Additionally, MG has a patent Systems of Acute Stroke Diagnosis licensed to GE Healthcare. All other authors declare no competing interests.
An unrestricted grant was provided to the University of Calgary (Calgary, AB, Canada) by Medtronic. The funder of the study had no role in study design, data collection, data analysis, data interpretation, writing of the report, or the decision to submit the paper for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
© 2018 Elsevier Ltd