TY - JOUR
T1 - Endovascular treatment effect diminishes with increasing thrombus perviousness
T2 - Pooled data from 7 trials on acute ischemic stroke
AU - Kappelhof, Manon
AU - Tolhuisen, Manon L.
AU - Treurniet, Kilian M.
AU - Dutra, Bruna G.
AU - Alves, Heitor
AU - Zhang, Guang
AU - Brown, Scott
AU - Muir, Keith W.
AU - Dávalos, Antoni
AU - Roos, Yvo B. W. E. M.
AU - Saver, Jeffrey L.
AU - Demchuk, Andrew M.
AU - Jovin, Tudor G.
AU - Bracard, Serge
AU - Campbell, Bruce C. V.
AU - van der Lugt, Aad
AU - Guillemin, Francis
AU - White, Philip
AU - Hill, Michael D.
AU - Dippel, Diederik W. J.
AU - Mitchell, Peter J.
AU - Goyal, Mayank
AU - Marquering, Henk A.
AU - Majoie, Charles B. L. M.
N1 - Funding Information: Dr Kappelhof reports MRCLEAN-NOIV coordinator. Dr Brown reports personal (University of Calgary, Medtronic). Dr Muir reports personal (Boehringer Ingelheim, Bayer, Daiichi Sankyo, Biogen, ReNeuron). Drs Roos and Marquering reports shareholder (Nico-Lab). Dr Saver reports personal (Medtronic). Dr Demchuk reports personal (Medtronic, Boehringer Ingelheim), patent (Circle NVI). Dr Jovin received personal (Ceronovus, Codman Neurovascular, Neuravi, Stryker, Fundacio Ictus), grants (Stryker Neurovascular, GE Healthcare), shares (Silk Road, Anaconda, Route 92, Blockade), other (Anaconda, Route92, Vizai, FreeOx, Corindus, Methinks, Contego Medical). Dr Campbell reports the following institutional (National Health and Medical Research Council, Royal Australasian College of Physicians, Royal Melbourne Hospital Foundation, National Heart Foundation, National Stroke Foundation of Australia, Medtronic). Dr van der Lugt received grants (GE Healthcare, Siemens Engineers, Thrombolytics Science Inc, Ceronovus, Penumbra, Stryker, Medtronic, AngioCare BV, Covidien/EV3, Medac GmbH/Lamepro, Dutch Heart Foundation, Thrombolytic Science Inc). Dr White reports the following institutional (Stryker, Penumbra, Medtronic), personal (Microvention). Dr Hill reports the following institutional (NoNO Inc, Boehringer Ingelheim), patent (Systems and Methods for Assisting in Decision-Making and Triaging for Acute Stroke Patients), director (Canadian Neuroscience Federation, Canadian Stroke Consortium, Circle Neurovascular). Dr Dippel reports the following institutional (Dutch Heart Foundation, AngioCare BV, Covidien/EV3, Medac GmbH/Lamepro, Penumbra, Top Medical/Concentric, Stryker, Ceronovus, Brain Foundation Netherlands, the Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences and Health, Medtronic). Dr Mitchell reports the following institutional (Medtronic, Stryker, Codman, Johnson & Johnson). Dr Goyal reports personal (Medtronic, Stryker, Microvention), patent (Systems of acute stroke diagnosis). Dr Majoie received grants (CardioVasculair Onderzoek Nederland/Dutch Heart Foundation, European Commission, Dutch Health Evaluation Program, Stryker, Toegepast Wetenschappelijk Instituut voor Neuromodulatie [TWIN] Foundation). Funding Information: The HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke) collaboration was funded by a grant to the University of Calgary from Medtronic LLC. Publisher Copyright: © 2021 Lippincott Williams and Wilkins. All rights reserved.
PY - 2021/11
Y1 - 2021/11
N2 - BACKGROUND AND PURPOSE: Thrombus perviousness estimates residual flow along a thrombus in acute ischemic stroke, based on radiological images, and may influence the benefit of endovascular treatment for acute ischemic stroke. We aimed to investigate potential endovascular treatment (EVT) effect modification by thrombus perviousness. METHODS: We included 443 patients with thin-slice imaging available, out of 1766 patients from the pooled HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke trials) data set of 7 randomized trials on EVT in the early window (most within 8 hours). Control arm patients (n=233) received intravenous alteplase if eligible (212/233; 91%). Intervention arm patients (n=210) received additional EVT (prior alteplase in 178/210; 85%). Perviousness was quantified by thrombus attenuation increase on admission computed tomography angiography compared with noncontrast computed tomography. Multivariable regression analyses were performed including multiplicative interaction terms between thrombus attenuation increase and treatment allocation. In case of significant interaction, subgroup analyses by treatment arm were performed. Our primary outcome was 90-day functional outcome (modified Rankin Scale score), resulting in an adjusted common odds ratio for a one-step shift towards improved outcome. Secondary outcomes were mortality, successful reperfusion (extended Thrombolysis in Cerebral Infarction score, 2B-3), and follow-up infarct volume (in mL). RESULTS: Increased perviousness was associated with improved functional outcome. After adding a multiplicative term of thrombus attenuation increase and treatment allocation, model fit improved significantly (P=0.03), indicating interaction between perviousness and EVT benefit. Control arm patients showed significantly better outcomes with increased perviousness (adjusted common odds ratio, 1.2 [95% CI, 1.1-1.3]). In the EVT arm, no significant association was found (adjusted common odds ratio, 1.0 [95% CI, 0.9-1.1]), and perviousness was not significantly associated with successful reperfusion. Follow-up infarct volume (12% [95% CI, 7.0-17] per 5 Hounsfield units) and chance of mortality (adjusted odds ratio, 0.83 [95% CI, 0.70-0.97]) decreased with higher thrombus attenuation increase in the overall population, without significant treatment interaction. CONCLUSIONS: Our study suggests that the benefit of best medical care including alteplase, compared with additional EVT, increases in patients with more pervious thrombi.
AB - BACKGROUND AND PURPOSE: Thrombus perviousness estimates residual flow along a thrombus in acute ischemic stroke, based on radiological images, and may influence the benefit of endovascular treatment for acute ischemic stroke. We aimed to investigate potential endovascular treatment (EVT) effect modification by thrombus perviousness. METHODS: We included 443 patients with thin-slice imaging available, out of 1766 patients from the pooled HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke trials) data set of 7 randomized trials on EVT in the early window (most within 8 hours). Control arm patients (n=233) received intravenous alteplase if eligible (212/233; 91%). Intervention arm patients (n=210) received additional EVT (prior alteplase in 178/210; 85%). Perviousness was quantified by thrombus attenuation increase on admission computed tomography angiography compared with noncontrast computed tomography. Multivariable regression analyses were performed including multiplicative interaction terms between thrombus attenuation increase and treatment allocation. In case of significant interaction, subgroup analyses by treatment arm were performed. Our primary outcome was 90-day functional outcome (modified Rankin Scale score), resulting in an adjusted common odds ratio for a one-step shift towards improved outcome. Secondary outcomes were mortality, successful reperfusion (extended Thrombolysis in Cerebral Infarction score, 2B-3), and follow-up infarct volume (in mL). RESULTS: Increased perviousness was associated with improved functional outcome. After adding a multiplicative term of thrombus attenuation increase and treatment allocation, model fit improved significantly (P=0.03), indicating interaction between perviousness and EVT benefit. Control arm patients showed significantly better outcomes with increased perviousness (adjusted common odds ratio, 1.2 [95% CI, 1.1-1.3]). In the EVT arm, no significant association was found (adjusted common odds ratio, 1.0 [95% CI, 0.9-1.1]), and perviousness was not significantly associated with successful reperfusion. Follow-up infarct volume (12% [95% CI, 7.0-17] per 5 Hounsfield units) and chance of mortality (adjusted odds ratio, 0.83 [95% CI, 0.70-0.97]) decreased with higher thrombus attenuation increase in the overall population, without significant treatment interaction. CONCLUSIONS: Our study suggests that the benefit of best medical care including alteplase, compared with additional EVT, increases in patients with more pervious thrombi.
KW - Cerebral infarction
KW - Decision making
KW - Reperfusion
KW - Stroke
KW - Thrombectomy
KW - Tissue-type plasminogen activator
UR - http://www.scopus.com/inward/record.url?scp=85118986989&partnerID=8YFLogxK
U2 - https://doi.org/10.1161/STROKEAHA.120.033124
DO - https://doi.org/10.1161/STROKEAHA.120.033124
M3 - Article
C2 - 34281377
SN - 0039-2499
VL - 52
SP - 3633
EP - 3641
JO - Stroke
JF - Stroke
IS - 11
ER -