Thrombectomy versus Medical Management in Mild Strokes due to Large Vessel Occlusion: Exploratory Analysis from the EXTEND-IA Trials and a Pooled International Cohort

for the PERFECT-MILD Collaborators

doi:10.1002/ana.26418

Thrombectomy versus Medical Management in Mild Strokes due to Large Vessel Occlusion: Exploratory Analysis from the EXTEND-IA Trials and a Pooled International Cohort

for the PERFECT-MILD Collaborators

Neurology

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

Objective: This study was undertaken to evaluate functional and safety outcomes for endovascular thrombectomy (EVT) versus medical management (MM) in patients with large vessel occlusion (LVO) and mild neurological deficits, stratified by perfusion imaging mismatch. Methods: The pooled cohort consisted of patients with National Institutes of Health Stroke Scale (NIHSS) < 6 and internal carotid artery (ICA), M1, or M2 occlusions from the Extending the Time for Thrombolysis in Emergecy Neurological Deficits - Intra-Arterial (EXTEND-IA) Trial, Tenecteplase vs Alteplase before Endovascular Thrombectomy in Ischemic Stroke (EXTEND-IA TNK) trials Part I/II and prospective data from 15 EVT centers from October 2010 to April 2020. RAPID software estimated ischemic core and mismatch. Patients receiving primary EVT (EVT_pri) were compared to those who received primary MM (MM_pri), including those who deteriorated and received rescue EVT, in overall and propensity score (PS)-matched cohorts. Patients were stratified by target mismatch (mismatch ratio ≥ 1.8 and mismatch volume ≥ 15ml). Primary outcome was functional independence (90-day modified Rankin Scale = 0–2). Secondary outcomes included safety (symptomatic intracerebral hemorrhage [sICH], neurological worsening, and mortality). Results: Of 540 patients, 286 (53%) received EVT_pri and demonstrated larger critically hypoperfused tissue (Tmax > 6 seconds) volumes (median [IQR]: 64 [26–96] ml vs MM_pri: 40 [14–76] ml, p < 0.001) and higher presentation NIHSS (median [IQR]: 4 [2–5] vs MM_pri: 3 [2–4], p < 0.001). Functional independence was similar (EVT_pri: 77.4% vs MM_pri: 75.6%, adjusted odds ratio [aOR] = 1.29, 95% confidence interval [CI] = 0.82–2.03, p = 0.27). EVT had worse safety regarding sICH (EVT_pri: 16.3% vs MM_pri: 1.3%, p < 0.001) and neurological worsening (EVT_pri: 19.6% vs MM_pri: 6.7%, p < 0.001). In 414 subjects (76.7%) with target mismatch, EVT was associated with improved functional independence (EVT_pri: 77.4% vs MM_pri: 72.7%, aOR = 1.68, 95% CI = 1.01–2.81, p = 0.048), whereas there was a trend toward less favorable outcomes with primary EVT (EVT_pri: 77.4% vs MM_pri: 83.3%, aOR = 0.39, 95% CI = 0.12–1.34, p = 0.13) without target mismatch (p_interaction = 0.06). Similar findings were observed in a propensity score-matched subpopulation. Interpretation: Overall, EVT was not associated with improved clinical outcomes in mild strokes due to LVO, and sICH was increased. However, in patients with target mismatch profile, EVT was associated with increased functional independence. Perfusion imaging may be helpful to select mild stroke patients for EVT. ANN NEUROL 2022;92:364–378.

Original language	English (US)
Pages (from-to)	364-378
Number of pages	15
Journal	Annals of Neurology
Volume	92
Issue number	3
DOIs	https://doi.org/10.1002/ana.26418
State	Published - Sep 2022

Bibliographical note

Funding Information:
The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not‐for‐profit sectors. The EXTEND‐IA, EXTEND‐IA TNK, and EXTEND‐IA TNK Part II trials were supported by grants from the Australian National Health and Medical Research Council of Australia, Royal Australasian College of Physicians, Royal Melbourne Hospital Foundation, National Heart Foundation of Australia, and National Stroke Foundation of Australia, and by infrastructure funding from the state government of Victoria. For EXTEND‐IA, the Solitaire FR device and trial infrastructure were provided under an unrestricted grant from Covidien. The EXTEND‐IA TNK trial was also supported by an unrestricted grant from Medtronic. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication.

Funding Information:
The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors. The EXTEND-IA, EXTEND-IA TNK, and EXTEND-IA TNK Part II trials were supported by grants from the Australian National Health and Medical Research Council of Australia, Royal Australasian College of Physicians, Royal Melbourne Hospital Foundation, National Heart Foundation of Australia, and National Stroke Foundation of Australia, and by infrastructure funding from the state government of Victoria. For EXTEND-IA, the Solitaire FR device and trial infrastructure were provided under an unrestricted grant from Covidien. The EXTEND-IA TNK trial was also supported by an unrestricted grant from Medtronic. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication. We thank iSchemaView for processing of perfusion imaging for the purpose of analysis.

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© 2022 American Neurological Association.

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@article{21ba8e4e53ef4bbea7baf32d801c7e90,

title = "Thrombectomy versus Medical Management in Mild Strokes due to Large Vessel Occlusion: Exploratory Analysis from the EXTEND-IA Trials and a Pooled International Cohort",

abstract = "Objective: This study was undertaken to evaluate functional and safety outcomes for endovascular thrombectomy (EVT) versus medical management (MM) in patients with large vessel occlusion (LVO) and mild neurological deficits, stratified by perfusion imaging mismatch. Methods: The pooled cohort consisted of patients with National Institutes of Health Stroke Scale (NIHSS) < 6 and internal carotid artery (ICA), M1, or M2 occlusions from the Extending the Time for Thrombolysis in Emergecy Neurological Deficits - Intra-Arterial (EXTEND-IA) Trial, Tenecteplase vs Alteplase before Endovascular Thrombectomy in Ischemic Stroke (EXTEND-IA TNK) trials Part I/II and prospective data from 15 EVT centers from October 2010 to April 2020. RAPID software estimated ischemic core and mismatch. Patients receiving primary EVT (EVTpri) were compared to those who received primary MM (MMpri), including those who deteriorated and received rescue EVT, in overall and propensity score (PS)-matched cohorts. Patients were stratified by target mismatch (mismatch ratio ≥ 1.8 and mismatch volume ≥ 15ml). Primary outcome was functional independence (90-day modified Rankin Scale = 0–2). Secondary outcomes included safety (symptomatic intracerebral hemorrhage [sICH], neurological worsening, and mortality). Results: Of 540 patients, 286 (53%) received EVTpri and demonstrated larger critically hypoperfused tissue (Tmax > 6 seconds) volumes (median [IQR]: 64 [26–96] ml vs MMpri: 40 [14–76] ml, p < 0.001) and higher presentation NIHSS (median [IQR]: 4 [2–5] vs MMpri: 3 [2–4], p < 0.001). Functional independence was similar (EVTpri: 77.4% vs MMpri: 75.6%, adjusted odds ratio [aOR] = 1.29, 95% confidence interval [CI] = 0.82–2.03, p = 0.27). EVT had worse safety regarding sICH (EVTpri: 16.3% vs MMpri: 1.3%, p < 0.001) and neurological worsening (EVTpri: 19.6% vs MMpri: 6.7%, p < 0.001). In 414 subjects (76.7%) with target mismatch, EVT was associated with improved functional independence (EVTpri: 77.4% vs MMpri: 72.7%, aOR = 1.68, 95% CI = 1.01–2.81, p = 0.048), whereas there was a trend toward less favorable outcomes with primary EVT (EVTpri: 77.4% vs MMpri: 83.3%, aOR = 0.39, 95% CI = 0.12–1.34, p = 0.13) without target mismatch (pinteraction = 0.06). Similar findings were observed in a propensity score-matched subpopulation. Interpretation: Overall, EVT was not associated with improved clinical outcomes in mild strokes due to LVO, and sICH was increased. However, in patients with target mismatch profile, EVT was associated with increased functional independence. Perfusion imaging may be helpful to select mild stroke patients for EVT. ANN NEUROL 2022;92:364–378.",

author = "{for the PERFECT-MILD Collaborators} and Amrou Sarraj and Albers, {Gregory W.} and Jordi Blasco and Arenillas, {Juan F.} and Marc Ribo and Hassan, {Ameer E.} and {de la Ossa}, {Natalia P{\'e}rez} and Wu, {Teddy Yuan Hao} and {Cardona Portela}, Pere and Abraham, {Michael G.} and Michael Chen and Laith Maali and Kleinig, {Timothy J.} and Dennis Cordato and Wallace, {Adam Nathan} and Schaafsma, {Joanna D.} and Navdeep Sangha and Gibson, {Daniel P.} and Blackburn, {Spiros L.} and {De Lera Alfonso}, Mercedes and Deep Pujara and Faris Shaker and McCullough-Hicks, {Margy E.} and {Moreno Negrete}, {Javier Luis} and Arturo Renu and James Beharry and Cecilia Cappelen-Smith and Luis Rodr{\'i}guez-Esparragoza and Marta Oliv{\'e}-Gadea and Manuel Requena and Tareq Almaghrabi and {Mendes Pereira}, Vitor and Clark Sitton and Sheryl Martin-Schild and Sarah Song and Henry Ma and Leonid Churilov and Mitchell, {Peter J.} and Parsons, {Mark W.} and Anthony Furlan and Grotta, {James C.} and Donnan, {Geoffrey A.} and Davis, {Stephen M.} and Campbell, {Bruce C.V.}",

note = "Funding Information: The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not‐for‐profit sectors. The EXTEND‐IA, EXTEND‐IA TNK, and EXTEND‐IA TNK Part II trials were supported by grants from the Australian National Health and Medical Research Council of Australia, Royal Australasian College of Physicians, Royal Melbourne Hospital Foundation, National Heart Foundation of Australia, and National Stroke Foundation of Australia, and by infrastructure funding from the state government of Victoria. For EXTEND‐IA, the Solitaire FR device and trial infrastructure were provided under an unrestricted grant from Covidien. The EXTEND‐IA TNK trial was also supported by an unrestricted grant from Medtronic. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication. Funding Information: The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors. The EXTEND-IA, EXTEND-IA TNK, and EXTEND-IA TNK Part II trials were supported by grants from the Australian National Health and Medical Research Council of Australia, Royal Australasian College of Physicians, Royal Melbourne Hospital Foundation, National Heart Foundation of Australia, and National Stroke Foundation of Australia, and by infrastructure funding from the state government of Victoria. For EXTEND-IA, the Solitaire FR device and trial infrastructure were provided under an unrestricted grant from Covidien. The EXTEND-IA TNK trial was also supported by an unrestricted grant from Medtronic. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication. We thank iSchemaView for processing of perfusion imaging for the purpose of analysis. Publisher Copyright: {\textcopyright} 2022 American Neurological Association.",

year = "2022",

month = sep,

doi = "10.1002/ana.26418",

language = "English (US)",

volume = "92",

pages = "364--378",

journal = "Annals of Neurology",

issn = "0364-5134",

publisher = "John Wiley and Sons Inc.",

number = "3",

}

TY - JOUR

T1 - Thrombectomy versus Medical Management in Mild Strokes due to Large Vessel Occlusion

T2 - Exploratory Analysis from the EXTEND-IA Trials and a Pooled International Cohort

AU - for the PERFECT-MILD Collaborators

AU - Sarraj, Amrou

AU - Albers, Gregory W.

AU - Blasco, Jordi

AU - Arenillas, Juan F.

AU - Ribo, Marc

AU - Hassan, Ameer E.

AU - de la Ossa, Natalia Pérez

AU - Wu, Teddy Yuan Hao

AU - Cardona Portela, Pere

AU - Abraham, Michael G.

AU - Chen, Michael

AU - Maali, Laith

AU - Kleinig, Timothy J.

AU - Cordato, Dennis

AU - Wallace, Adam Nathan

AU - Schaafsma, Joanna D.

AU - Sangha, Navdeep

AU - Gibson, Daniel P.

AU - Blackburn, Spiros L.

AU - De Lera Alfonso, Mercedes

AU - Pujara, Deep

AU - Shaker, Faris

AU - McCullough-Hicks, Margy E.

AU - Moreno Negrete, Javier Luis

AU - Renu, Arturo

AU - Beharry, James

AU - Cappelen-Smith, Cecilia

AU - Rodríguez-Esparragoza, Luis

AU - Olivé-Gadea, Marta

AU - Requena, Manuel

AU - Almaghrabi, Tareq

AU - Mendes Pereira, Vitor

AU - Sitton, Clark

AU - Martin-Schild, Sheryl

AU - Song, Sarah

AU - Ma, Henry

AU - Churilov, Leonid

AU - Mitchell, Peter J.

AU - Parsons, Mark W.

AU - Furlan, Anthony

AU - Grotta, James C.

AU - Donnan, Geoffrey A.

AU - Davis, Stephen M.

AU - Campbell, Bruce C.V.

N1 - Funding Information: The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not‐for‐profit sectors. The EXTEND‐IA, EXTEND‐IA TNK, and EXTEND‐IA TNK Part II trials were supported by grants from the Australian National Health and Medical Research Council of Australia, Royal Australasian College of Physicians, Royal Melbourne Hospital Foundation, National Heart Foundation of Australia, and National Stroke Foundation of Australia, and by infrastructure funding from the state government of Victoria. For EXTEND‐IA, the Solitaire FR device and trial infrastructure were provided under an unrestricted grant from Covidien. The EXTEND‐IA TNK trial was also supported by an unrestricted grant from Medtronic. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication. Funding Information: The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors. The EXTEND-IA, EXTEND-IA TNK, and EXTEND-IA TNK Part II trials were supported by grants from the Australian National Health and Medical Research Council of Australia, Royal Australasian College of Physicians, Royal Melbourne Hospital Foundation, National Heart Foundation of Australia, and National Stroke Foundation of Australia, and by infrastructure funding from the state government of Victoria. For EXTEND-IA, the Solitaire FR device and trial infrastructure were provided under an unrestricted grant from Covidien. The EXTEND-IA TNK trial was also supported by an unrestricted grant from Medtronic. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication. We thank iSchemaView for processing of perfusion imaging for the purpose of analysis. Publisher Copyright: © 2022 American Neurological Association.

PY - 2022/9

Y1 - 2022/9

N2 - Objective: This study was undertaken to evaluate functional and safety outcomes for endovascular thrombectomy (EVT) versus medical management (MM) in patients with large vessel occlusion (LVO) and mild neurological deficits, stratified by perfusion imaging mismatch. Methods: The pooled cohort consisted of patients with National Institutes of Health Stroke Scale (NIHSS) < 6 and internal carotid artery (ICA), M1, or M2 occlusions from the Extending the Time for Thrombolysis in Emergecy Neurological Deficits - Intra-Arterial (EXTEND-IA) Trial, Tenecteplase vs Alteplase before Endovascular Thrombectomy in Ischemic Stroke (EXTEND-IA TNK) trials Part I/II and prospective data from 15 EVT centers from October 2010 to April 2020. RAPID software estimated ischemic core and mismatch. Patients receiving primary EVT (EVTpri) were compared to those who received primary MM (MMpri), including those who deteriorated and received rescue EVT, in overall and propensity score (PS)-matched cohorts. Patients were stratified by target mismatch (mismatch ratio ≥ 1.8 and mismatch volume ≥ 15ml). Primary outcome was functional independence (90-day modified Rankin Scale = 0–2). Secondary outcomes included safety (symptomatic intracerebral hemorrhage [sICH], neurological worsening, and mortality). Results: Of 540 patients, 286 (53%) received EVTpri and demonstrated larger critically hypoperfused tissue (Tmax > 6 seconds) volumes (median [IQR]: 64 [26–96] ml vs MMpri: 40 [14–76] ml, p < 0.001) and higher presentation NIHSS (median [IQR]: 4 [2–5] vs MMpri: 3 [2–4], p < 0.001). Functional independence was similar (EVTpri: 77.4% vs MMpri: 75.6%, adjusted odds ratio [aOR] = 1.29, 95% confidence interval [CI] = 0.82–2.03, p = 0.27). EVT had worse safety regarding sICH (EVTpri: 16.3% vs MMpri: 1.3%, p < 0.001) and neurological worsening (EVTpri: 19.6% vs MMpri: 6.7%, p < 0.001). In 414 subjects (76.7%) with target mismatch, EVT was associated with improved functional independence (EVTpri: 77.4% vs MMpri: 72.7%, aOR = 1.68, 95% CI = 1.01–2.81, p = 0.048), whereas there was a trend toward less favorable outcomes with primary EVT (EVTpri: 77.4% vs MMpri: 83.3%, aOR = 0.39, 95% CI = 0.12–1.34, p = 0.13) without target mismatch (pinteraction = 0.06). Similar findings were observed in a propensity score-matched subpopulation. Interpretation: Overall, EVT was not associated with improved clinical outcomes in mild strokes due to LVO, and sICH was increased. However, in patients with target mismatch profile, EVT was associated with increased functional independence. Perfusion imaging may be helpful to select mild stroke patients for EVT. ANN NEUROL 2022;92:364–378.

AB - Objective: This study was undertaken to evaluate functional and safety outcomes for endovascular thrombectomy (EVT) versus medical management (MM) in patients with large vessel occlusion (LVO) and mild neurological deficits, stratified by perfusion imaging mismatch. Methods: The pooled cohort consisted of patients with National Institutes of Health Stroke Scale (NIHSS) < 6 and internal carotid artery (ICA), M1, or M2 occlusions from the Extending the Time for Thrombolysis in Emergecy Neurological Deficits - Intra-Arterial (EXTEND-IA) Trial, Tenecteplase vs Alteplase before Endovascular Thrombectomy in Ischemic Stroke (EXTEND-IA TNK) trials Part I/II and prospective data from 15 EVT centers from October 2010 to April 2020. RAPID software estimated ischemic core and mismatch. Patients receiving primary EVT (EVTpri) were compared to those who received primary MM (MMpri), including those who deteriorated and received rescue EVT, in overall and propensity score (PS)-matched cohorts. Patients were stratified by target mismatch (mismatch ratio ≥ 1.8 and mismatch volume ≥ 15ml). Primary outcome was functional independence (90-day modified Rankin Scale = 0–2). Secondary outcomes included safety (symptomatic intracerebral hemorrhage [sICH], neurological worsening, and mortality). Results: Of 540 patients, 286 (53%) received EVTpri and demonstrated larger critically hypoperfused tissue (Tmax > 6 seconds) volumes (median [IQR]: 64 [26–96] ml vs MMpri: 40 [14–76] ml, p < 0.001) and higher presentation NIHSS (median [IQR]: 4 [2–5] vs MMpri: 3 [2–4], p < 0.001). Functional independence was similar (EVTpri: 77.4% vs MMpri: 75.6%, adjusted odds ratio [aOR] = 1.29, 95% confidence interval [CI] = 0.82–2.03, p = 0.27). EVT had worse safety regarding sICH (EVTpri: 16.3% vs MMpri: 1.3%, p < 0.001) and neurological worsening (EVTpri: 19.6% vs MMpri: 6.7%, p < 0.001). In 414 subjects (76.7%) with target mismatch, EVT was associated with improved functional independence (EVTpri: 77.4% vs MMpri: 72.7%, aOR = 1.68, 95% CI = 1.01–2.81, p = 0.048), whereas there was a trend toward less favorable outcomes with primary EVT (EVTpri: 77.4% vs MMpri: 83.3%, aOR = 0.39, 95% CI = 0.12–1.34, p = 0.13) without target mismatch (pinteraction = 0.06). Similar findings were observed in a propensity score-matched subpopulation. Interpretation: Overall, EVT was not associated with improved clinical outcomes in mild strokes due to LVO, and sICH was increased. However, in patients with target mismatch profile, EVT was associated with increased functional independence. Perfusion imaging may be helpful to select mild stroke patients for EVT. ANN NEUROL 2022;92:364–378.

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DO - 10.1002/ana.26418

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JF - Annals of Neurology

IS - 3

ER -

Thrombectomy versus Medical Management in Mild Strokes due to Large Vessel Occlusion: Exploratory Analysis from the EXTEND-IA Trials and a Pooled International Cohort

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