Background: CT perfusion (CTP) and diffusion or perfusion MRI might assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of irreversibly injured ischaemic core and potentially salvageable penumbra volumes were associated with functional outcome and whether they interacted with the treatment effect of endovascular thrombectomy on functional outcome. Methods: In this systematic review and meta-analysis, the HERMES collaboration pooled patient-level data from all randomised controlled trials that compared endovascular thrombectomy (predominantly using stent retrievers) with standard medical therapy in patients with anterior circulation ischaemic stroke, published in PubMed from Jan 1, 2010, to May 31, 2017. The primary endpoint was functional outcome, assessed by the modified Rankin Scale (mRS) at 90 days after stroke. Ischaemic core was estimated, before treatment with either endovascular thrombectomy or standard medical therapy, by CTP as relative cerebral blood flow less than 30% of normal brain blood flow or by MRI as an apparent diffusion coefficient less than 620 μm2/s. Critically hypoperfused tissue was estimated as the volume of tissue with a CTP time to maximum longer than 6 s. Mismatch volume (ie, the estimated penumbral volume) was calculated as critically hypoperfused tissue volume minus ischaemic core volume. The association of ischaemic core and penumbral volumes with 90-day mRS score was analysed with multivariable logistic regression (functional independence, defined as mRS score 0–2) and ordinal logistic regression (functional improvement by at least one mRS category) in all patients and in a subset of those with more than 50% endovascular reperfusion, adjusted for baseline prognostic variables. The meta-analysis was prospectively designed by the HERMES executive committee, but not registered. Findings: We identified seven studies with 1764 patients, all of which were included in the meta-analysis. CTP was available and assessable for 591 (34%) patients and diffusion MRI for 309 (18%) patients. Functional independence was worse in patients who had CTP versus those who had diffusion MRI, after adjustment for ischaemic core volume (odds ratio [OR] 0·47 [95% CI 0·30–0·72], p=0·0007), so the imaging modalities were not pooled. Increasing ischaemic core volume was associated with reduced likelihood of functional independence (CTP OR 0·77 [0·69–0·86] per 10 mL, pinteraction=0·29; diffusion MRI OR 0·87 [0·81–0·94] per 10 mL, pinteraction=0·94). Mismatch volume, examined only in the CTP group because of the small numbers of patients who had perfusion MRI, was not associated with either functional independence or functional improvement. In patients with CTP with more than 50% endovascular reperfusion (n=186), age, ischaemic core volume, and imaging-to-reperfusion time were independently associated with functional improvement. Risk of bias between studies was generally low. Interpretation: Estimated ischaemic core volume was independently associated with functional independence and functional improvement but did not modify the treatment benefit of endovascular thrombectomy over standard medical therapy for improved functional outcome. Combining ischaemic core volume with age and expected imaging-to-reperfusion time will improve assessment of prognosis and might inform endovascular thrombectomy treatment decisions. Funding: Medtronic.
Bibliographical noteFunding Information:
BCVC reports research support from the National Health and Medical Research Council of Australia (GNT1043242 and GNT1035688) , Royal Australasian College of Physicians, Royal Melbourne Hospital Foundation, National Heart Foundation, National Stroke Foundation of Australia, and unrestricted grant funding for the EXTEND-IA trial to the Florey Institute of Neuroscience and Mental Health from Covidien (Medtronic). CBLMM reports personal fees paid to his institution from Stryker. GWA reports research support from the National Institutes of Health (U01NS092076 and 1U10NS086487) , equity interest in iSchemaView, and consulting fees from Medtronic and iSchemaView. BKM was a member of the steering and executive committee for the ESCAPE trial, which received support from Covidien (Medtronic), was site principal investigator for the SOCRATES trial, which was sponsored by AstraZeneca, has received honoraria from Penumbra, has a provisional patent (62/086077) for triaging systems in ischaemic stroke, and has research funding from the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Alberta Innovates—Health Solutions, and the Hotchkiss Brain Institute and the Faculty of Medicine, University of Calgary. WHvZ reports personal fees paid to his institution by Stryker and Cerenovus. AMD reports grant funding from Medtronic for the ESCAPE trial and personal fees from Medtronic. PW reports grant funding to the University of Glasgow for the PISTE trial from Medtronic and Codman as well as grants from the Stroke Association (TSA 2011/06) and the National Institute of Health Research (NIHR) Health Technology Assessment programme (HTA 14.08.47), grants and personal fees from Microvention Terumo and personal fees from Stryker and Codman. AD reports grant funding for the REVASCAT trial and personal fees from Medtronic. AvdL reports grant funding to his institution from Stryker, Medtronic and Penumbra and personal fees paid to his institution from Stryker. HAM is co-founder of Nico-lab and holds stock. GAD reports travel support from Boehringer Ingelheim and personal fees from Boehringer Ingelheim, AstraZeneca, Bristol Meyers-Squibb, and Merck Sharp & Dohme for serving on advisory boards. JS reports grants from Canadian Institutes of Health Research and the Faculty of Medicine, Dalhousie University. AB reports personal fees from Medtronic and Stryker. RJ reports personal fees for consultancy from Covidien/Medtronic Neurovascular. EIL reports personal fees from Covidien (Medtronic), Abbott, and personal fees and stock ownership in Blockade Medical LLC. In addition, EIL renders expert legal opinion for different cases in his expertise as a neurosurgeon for attorneys. OAB reports personal fees from Stryker (paid to institution) for consultancy. SMD reports personal fees from Medtronic and Boehringer Ingelheim. SBro reports personal fees from Medtronic and the University of Calgary. KWM has received personal fees for consultancy from Medtronic. The University of Glasgow received grant support for the PISTE trial from Medtronic and Codman as well as grants from the Stroke Association (TSA 2011/06) and NIHR Health Technology Assessment programme (HTA 14·08·47). DWJD reports grants from the Dutch Heart Foundation, AngioCare BV, Medtronic/Covidien/EV3, MEDAC Gmbh/LAMEPRO, Penumbra, Top Medical/Concentric, and Stryker, and his institution received consultancy fees from Stryker, Bracco Imaging, and Servier. MG reports grants from Medtronic and Stryker, personal fees from Medtronic, Stryker, Microvention and GE Healthcare; MG also has a patent systems and methods for diagnosing strokes (PCT/CA2013/000761) licensed to GE Healthcare. 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 received payments on the basis of clinical trial contracts for the number of subjects enrolled; reports receiving contracted hourly payments and travel reimbursement from Covidien, Medtronic/Abbott, Stryker, and Neuravi/Abbott, and stock options from Rapid Medical, for service on Trial Steering Committees, advising on rigorous trial design and conduct. The University of California has patent rights in retrieval devices for stroke. TGJ has received personal fees for consultancy from Codman Neurovascular and Neuravi, holds stock in Silk Road, Anaconda, Route 92, FreeOx Biotech and Blockade; has acted as an unpaid consultant to Stryker as principal investigator of the DAWN trial. MDH reports unrestricted grant funding for the ESCAPE trial to University of Calgary from Covidien (Medtronic), and active or in-kind support consortium of public or 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); personal fees from Merck, and non-financial support (drugs for the TEMPO-1 trial) from Hoffmann-La Roche Canada Ltd; MDH also has a patent systems and methods for assisting in decision-making and triaging for acute stroke patients pending to US patent office number: 62/086,077 and owns stock in Calgary Scientific, a company that focuses on medical imaging software. PJM reports unrestricted research grants to his institution from Codman Johnson and Johnson, Medtronic, and Stryker and has served as an unpaid consultant to Codman Johnson and Johnson. All other authors declare no competing interests.
© 2019 Elsevier Ltd