Tudor G Jovin1, Raul G Nogueira2, Maarten G Lansberg3, Andrew M Demchuk4, Sheila O Martins5, J Mocco6, Marc Ribo7, Ashutosh P Jadhav8, Santiago Ortega-Gutierrez9, Michael D Hill10, Fabricio O Lima11, Diogo C Haussen2, Scott Brown12, Mayank Goyal4, Adnan H Siddiqui13, Jeremy J Heit14, Bijoy K Menon15, Stephanie Kemp3, Ron Budzik16, Xabier Urra17, Michael P Marks14, Vincent Costalat18, David S Liebeskind19, Gregory W Albers3. 1. Department of Neurology, Cooper University Health Care, Camden, NJ, USA; Cooper Medical School of Rowan University, Camden, NJ, USA. Electronic address: jovin-tudor@cooperhealth.edu. 2. Marcus Stroke and Neuroscience Center, Grady Memorial Hospital, Atlanta, GA, USA; Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA. 3. Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, CA, USA. 4. Department of Radiology and Clinical Neurosciences, Calgary Stroke Program, Cumming School of Medicine, University of Calgary, AB, Canada. 5. Department of Neurology, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 6. Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 7. Stroke Unit, Department of Neurology, Vall d'Hebron Research Institute, Barcelona, Spain. 8. Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ, USA. 9. Department of Neurology, Neurosurgery and Radiology, University of Iowa Healthcare, Iowa City, IA, USA. 10. Department of Clinical Neurosciences and CommunityHealth Sciences, Hotchkiss Brain Institute, Calgary Stroke Program, Cumming School of Medicine, University of Calgary, AB, Canada; Department of Radiology and Medicine, Hotchkiss Brain Institute, Calgary Stroke Program, Cumming School of Medicine, University of Calgary, AB, Canada. 11. Hospital Geral de Fortaleza, Fortaleza, Brazil. 12. BRIGHT Research Partners, Minneapolis, MN, USA. 13. Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA; Gates Vascular Institute at Kaleida Health, Buffalo, NY, USA. 14. Department of Radiology and Neurosurgery, NeuroInterventional Radiology Section, Stanford University Medical Center, Stanford, CA, USA. 15. Department of Clinical Neurosciences and CommunityHealth Sciences, Hotchkiss Brain Institute, Calgary Stroke Program, Cumming School of Medicine, University of Calgary, AB, Canada. 16. Radiology, Riverside Radiology and Interventional Associates, Ohio Health Riverside Methodist Hospital, Columbus, OH, USA. 17. Department of Neurology, Hospital Clínic, Barcelona, Spain. 18. Department of Neuroradiology, Hôpital Gui-de-Chauliac, Montpellier, France. 19. Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Abstract
BACKGROUND: Trials examining the benefit of thrombectomy in anterior circulation proximal large vessel occlusion stroke have enrolled patients considered to have salvageable brain tissue, who were randomly assigned beyond 6 h and (depending on study protocol) up to 24 h from time last seen well. We aimed to estimate the benefit of thrombectomy overall and in prespecified subgroups through individual patient data meta-analysis. METHODS: We did a systematic review and individual patient data meta-analysis between Jan 1, 2010, and March 1, 2021, of randomised controlled trials of endovascular stroke therapy. In the Analysis Of Pooled Data From Randomized Studies Of Thrombectomy More Than 6 Hours After Last Known Well (AURORA) collaboration, the primary outcome was disability on the modified Rankin Scale (mRS) at 90 days, analysed by ordinal logistic regression. Key safety outcomes were symptomatic intracerebral haemorrhage and mortality within 90 days. FINDINGS: Patient level data from 505 individuals (n=266 intervention, n=239 control; mean age 68·6 years [SD 13·7], 259 [51·3%] women) were included from six trials that met inclusion criteria of 17 screened published randomised trials. Primary outcome analysis showed a benefit of thrombectomy with an unadjusted common odds ratio (OR) of 2·42 (95% CI 1·76-3·33; p<0·0001) and an adjusted common OR (for age, gender, baseline stroke severity, extent of infarction on baseline head CT, and time from onset to random assignment) of 2·54 (1·83-3·54; p<0·0001). Thrombectomy was associated with higher rates of independence in activities of daily living (mRS 0-2) than best medical therapy alone (122 [45·9%] of 266 vs 46 [19·3%] of 238; p<0·0001). No significant difference between intervention and control groups was found when analysing either 90-day mortality (44 [16·5%] of 266 vs 46 [19·3%] of 238) or symptomatic intracerebral haemorrhage (14 [5·3%] of 266 vs eight [3·3%] of 239). No heterogeneity of treatment effect was noted across subgroups defined by age, gender, baseline stroke severity, vessel occlusion site, baseline Alberta Stroke Program Early CT Score, and mode of presentation; treatment effect was stronger in patients randomly assigned within 12-24 h (common OR 5·86 [95% CI 3·14-10·94]) than those randomly assigned within 6-12 h (1·76 [1·18-2·62]; pinteraction=0·0087). INTERPRETATION: These findings strengthen the evidence for benefit of endovascular thrombectomy in patients with evidence of reversible cerebral ischaemia across the 6-24 h time window and are relevant to clinical practice. Our findings suggest that in these patients, thrombectomy should not be withheld on the basis of mode of presentation or of the point in time of presentation within the 6-24 h time window. FUNDING: Stryker Neurovascular.
BACKGROUND: Trials examining the benefit of thrombectomy in anterior circulation proximal large vessel occlusion stroke have enrolled patients considered to have salvageable brain tissue, who were randomly assigned beyond 6 h and (depending on study protocol) up to 24 h from time last seen well. We aimed to estimate the benefit of thrombectomy overall and in prespecified subgroups through individual patient data meta-analysis. METHODS: We did a systematic review and individual patient data meta-analysis between Jan 1, 2010, and March 1, 2021, of randomised controlled trials of endovascular stroke therapy. In the Analysis Of Pooled Data From Randomized Studies Of Thrombectomy More Than 6 Hours After Last Known Well (AURORA) collaboration, the primary outcome was disability on the modified Rankin Scale (mRS) at 90 days, analysed by ordinal logistic regression. Key safety outcomes were symptomatic intracerebral haemorrhage and mortality within 90 days. FINDINGS: Patient level data from 505 individuals (n=266 intervention, n=239 control; mean age 68·6 years [SD 13·7], 259 [51·3%] women) were included from six trials that met inclusion criteria of 17 screened published randomised trials. Primary outcome analysis showed a benefit of thrombectomy with an unadjusted common odds ratio (OR) of 2·42 (95% CI 1·76-3·33; p<0·0001) and an adjusted common OR (for age, gender, baseline stroke severity, extent of infarction on baseline head CT, and time from onset to random assignment) of 2·54 (1·83-3·54; p<0·0001). Thrombectomy was associated with higher rates of independence in activities of daily living (mRS 0-2) than best medical therapy alone (122 [45·9%] of 266 vs 46 [19·3%] of 238; p<0·0001). No significant difference between intervention and control groups was found when analysing either 90-day mortality (44 [16·5%] of 266 vs 46 [19·3%] of 238) or symptomatic intracerebral haemorrhage (14 [5·3%] of 266 vs eight [3·3%] of 239). No heterogeneity of treatment effect was noted across subgroups defined by age, gender, baseline stroke severity, vessel occlusion site, baseline Alberta Stroke Program Early CT Score, and mode of presentation; treatment effect was stronger in patients randomly assigned within 12-24 h (common OR 5·86 [95% CI 3·14-10·94]) than those randomly assigned within 6-12 h (1·76 [1·18-2·62]; pinteraction=0·0087). INTERPRETATION: These findings strengthen the evidence for benefit of endovascular thrombectomy in patients with evidence of reversible cerebral ischaemia across the 6-24 h time window and are relevant to clinical practice. Our findings suggest that in these patients, thrombectomy should not be withheld on the basis of mode of presentation or of the point in time of presentation within the 6-24 h time window. FUNDING: Stryker Neurovascular.
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