Mayank Goyal1, Bijoy K Menon1, Wim H van Zwam2, Diederik W J Dippel3, Peter J Mitchell4, Andrew M Demchuk1, Antoni Dávalos5, Charles B L M Majoie6, Aad van der Lugt3, Maria A de Miquel7, Geoffrey A Donnan8, Yvo B W E M Roos6, Alain Bonafe9, Reza Jahan10, Hans-Christoph Diener11, Lucie A van den Berg6, Elad I Levy12, Olvert A Berkhemer6, Vitor M Pereira13, Jeremy Rempel14, Mònica Millán15, Stephen M Davis16, Daniel Roy17, John Thornton18, Luis San Román19, Marc Ribó20, Debbie Beumer2, Bruce Stouch21, Scott Brown22, Bruce C V Campbell16, Robert J van Oostenbrugge2, Jeffrey L Saver23, Michael D Hill1, Tudor G Jovin24. 1. Departments of Clinical Neuroscience and Radiology, Hotchkiss Brain Institute, Cummings School of Medicine, University of Calgary, Calgary, AB, Canada. 2. Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, Netherlands. 3. Erasmus MC University Medical Center, Rotterdam, Netherlands. 4. Department of Radiology, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia. 5. Hospital Germans Trias y Pujol, Barcelona, Spain. 6. Academic Medical Center, Amsterdam, Netherlands. 7. Hospital de Bellvitge, Barcelona, Spain. 8. Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia. 9. Hospital Guy de Chaulliac, Montpellier, France. 10. UCLA Medical Center, Los Angeles, CA, USA. 11. Department of Neurology, University Hospital Essen, Essen, Germany. 12. State University of New York, Buffalo, Buffalo, NY, USA. 13. University of Toronto, Toronto, ON, Canada. 14. University of Edmonton, Edmonton, AB, Canada. 15. Hospital Germans Trials y Pujol, Barcelona, Spain. 16. Department of Medicine and Neurology, Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia. 17. CHUM Notre-Dame Hospital, Montreal, QC, Canada. 18. Beaumont Hospital, Dublin, Ireland. 19. Hospital Clinic, Barcelona, Spain. 20. Hospital Vall d'Hebron, Barcelona, Spain. 21. Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA. 22. Altair Biostatistics, St Louis Park, MN, USA. 23. David Geffen School of Medicine, University of Los Angeles, Los Angeles, CA, USA. 24. University of Pittsburgh Medical Center Stroke Institute, Presbyterian University Hospital, Pittsburgh, PA, USA. Electronic address: jovintg@upmc.edu.
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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Medtronic.
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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Medtronic.
Authors: James E Siegler; Steven R Messé; Heidi Sucharew; Scott E Kasner; Tapan Mehta; Niraj Arora; Amy K Starosciak; Felipe De Los Rios La Rosa; Natasha R Barnhill; Akshitkumar M Mistry; Kishan Patel; Salman Assad; Amjad Tarboosh; Katarina Dakay; Jeff Wagner; Alicia Bennett; Bharathi Jagadeesan; Christopher Streib; Stewart A Weber; Rohan Chitale; John J Volpi; Stephan A Mayer; Shadi Yaghi; Mahesh V Jayaraman; Pooja Khatri; Eva A Mistry Journal: J Neuroimaging Date: 2019-11-24 Impact factor: 2.486