Mediation of the Relationship Between Endovascular Therapy and Functional Outcome by Follow-up Infarct Volume in Patients With Acute Ischemic Stroke

被引：104

作者：

Boers, Anna M. M. ^{[1
,2
,3
]}

Jansen, Ivo G. H. ^{[1
,2
]}

Brown, Scott ^{[4
]}

Lingsma, Hester F. ^{[5
]}

Beenen, Ludo F. M. ^{[2
]}

Devlin, Thomas G. ^{[6
]}

San Roman, Luis ^{[7
]}

Heo, Ji-Hoe ^{[8
]}

Ribo, Marc ^{[9
]}

Almekhlafi, Mohammed A. ^{[10
]}

Liebeskind, David S. ^{[11
]}

Teitelbaum, Jeanne ^{[12
]}

Cuadras, Patricia ^{[13
]}

de Rochemont, Richard du Mesnil ^{[14
]}

Beaumont, Marine ^{[15
,16
]}

Brown, Martin M. ^{[17
]}

Yoo, Albert J. ^{[18
]}

Donnan, Geoffrey A. ^{[19
]}

Mas, Jean Louis ^{[20
,21
]}

Oppenheim, Catherine ^{[22
,23
]}

Dowling, Richard J. ^{[24
]}

Moulin, Thierry ^{[25
]}

Agrinier, Nelly ^{[26
]}

Lopes, Demetrius K. ^{[27
]}

Aja Rodriguez, Lucia ^{[28
]}

Compagne, Kars C. J. ^{[29
,30
]}

Al-Ajlan, Fahad S. ^{[31
]}

Madigan, Jeremy ^{[32
]}

Albers, Gregory W. ^{[33
]}

Soize, Sebastien ^{[34
]}

Blasco, Jordi ^{[7
]}

Davis, Stephen M. ^{[35
]}

Nogueira, Raul G. ^{[36
]}

Davalos, Antoni ^{[37
]}

Menon, Bijoy K. ^{[38
]}

van der Lugt, Aad ^{[29
]}

Muir, Keith W. ^{[39
]}

Roos, Yvo B. W. E. M. ^{[40
]}

White, Phil ^{[41
]}

Mitchell, Peter J. ^{[24
]}

Demchuk, Andrew M. ^{[38
]}

van Zwam, Wim H. ^{[42
]}

Jovin, Tudor G. ^{[43
]}

van Oostenbrugge, Robert J. ^{[44
]}

Dippel, Diederik W. J. ^{[30
]}

Campbell, Bruce C. V. ^{[35
]}

Guillemin, Francis ^{[26
]}

Bracard, Serge ^{[45
,46
]}

Hill, Michael D. ^{[38
]}

Goyal, Mayank ^{[38
]}

机构：

[1] Univ Amsterdam, Med Ctr, AMC, Dept Biomed Engn & Phys, Amsterdam, Netherlands

[2] Univ Amsterdam, Med Ctr, Dept Radiol & Nucl Med, AMC, Amsterdam, Netherlands

[3] Univ Twente, Dept Robot & Mechatron, Enschede, Netherlands

[4] Altair Biostat, Mooresville, NC USA

[5] Erasmus Univ, Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands

[6] Univ Tennessee, Erlanger Hosp, Dept Neurol, Chattanooga, TN USA

[7] Hosp Clin Barcelona, Dept Intervent Neuroradiol, Barcelona, Catalonia, Spain

[8] Yonsei Univ, Dept Neurol, Seoul, South Korea

[9] Vall dHebron Univ Hosp, Dept Neurol, Barcelona, Catalonia, Spain

[10] King Abdulaziz Univ, Fac Med, Dept Neurol, Jeddah, Saudi Arabia

[11] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA

[12] McGill Univ, Montreal Neurol Inst & Hosp, Dept Neurol & Neurosurg, Montreal, PQ, Canada

[13] Univ Autonoma Barcelona, Hosp Germans Trias & Pujol, Dept Radiol, Barcelona, Catalonia, Spain

[14] Goethe Univ Frankfurt, Goethe Univ Hosp, Dept Radiol, Frankfurt, Germany

[15] Univ Lorraine, Inserm CIC IT 1433, Nancy, France

[16] Univ Hosp Nancy, Nancy, France

[17] UCL, Inst Neurol, London, England

[18] Texas Stroke Inst, Div Neurointervent, Dallas, TX USA

[19] Univ Melbourne, Royal Melbourne Hosp, Melbourne Brain Ctr, Florey Inst Neurosci & Mental Hlth, Melbourne, Vic, Australia

[20] St Anne Hosp, Dept Neurol, Paris, France

[21] Paris Descartes Univ, INSERM U894, Paris, France

[22] St Anne Hosp, Dept Neuroradiol, Paris, France

[23] Paris Descartes Univ, INSERM U894, Paris, France

[24] Univ Melbourne, Royal Melbourne Hosp, Melbourne Brain Ctr, Dept Radiol, Melbourne, Vic, Australia

[25] Univ Franche Comte, Univ Hosp Besancon, Dept Neurol, Besancon, France

[26] Univ Lorraine, Ctr Hosp Reg & Univ Nancy, INSERM, CIC1433 Epidemiol Clin, Nancy, France

[27] Rush Univ, Med Ctr, Dept Neurol Surg, Chicago, IL 60612 USA

[28] Hosp Univ Bellvitge, Dept Neuroradiol, Barcelona, Catalonia, Spain

[29] Erasmus Univ, Med Ctr, Dept Radiol & Nucl Med, Rotterdam, Netherlands

[30] Erasmus Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands

[31] King Faisal Specialist Hosp & Res Ctr, Dept Neurosci, Riyadh, Saudi Arabia

[32] St Georges Univ Hosp, London, England

[33] Stanford Stroke Ctr, Dept Neurol, Palo Alto, CA USA

[34] Univ Hosp Reims, Dept Neuroradiol, Reims, France

[35] Univ Melbourne, Royal Melbourne Hosp, Melbourne Brain Ctr, Dept Med & Neurol, Melbourne, Vic, Australia

[36] Emory Univ, Sch Med, Grady Mem Hosp, Dept Neurol Neurosurg & Radiol, Atlanta, GA USA

[37] Univ Autonoma Barcelona, Hosp Germans Trias & Pujol, Dept Neurosci, Barcelona, Catalonia, Spain

[38] Univ Calgary, Foothills Hosp, Cumming Sch Med, Dept Clin Neurosci,Hotchkiss Brain Inst, Calgary, AB, Canada

[39] Univ Glasgow, Queen Elizabeth Univ Hosp, Inst Neurosci & Psychol, Glasgow, Lanark, Scotland

[40] Univ Amsterdam, Med Ctr, AMC, Dept Neurol, Amsterdam, Netherlands

[41] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne, Tyne & Wear, England

[42] Maastricht Univ, Med Ctr, Cardiovasc Res Inst Maastricht CARIM, Dept Radiol, Maastricht, Netherlands

[43] Univ Pittsburgh, Med Ctr, Dept Neurol, Stroke Inst, Pittsburgh, PA USA

[44] Maastricht Univ, Med Ctr, Cardiovasc Res Inst Maastricht CARIM, Dept Neurol, Maastricht, Netherlands

[45] Univ Lorraine, INSERM U947, Dept Diagnost & Intervent Neuroradiol, Nancy, France

[46] Univ Hosp Nancy, Nancy, France

来源：

JAMA NEUROLOGY | 2019年 / 76卷 / 02期

关键词：

CT SCANS; THROMBECTOMY; RECANALIZATION; REPERFUSION; INSIGHTS; 24-HOUR;

D O I：

10.1001/jamaneurol.2018.3661

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

IMPORTANCE The positive treatment effect of endovascular therapy (EVT) is assumed to be caused by the preservation of brain tissue. It remains unclear to what extent the treatment-related reduction in follow-up infarct volume (FIV) explains the improved functional outcome after EVT in patients with acute ischemic stroke. OBJECTIVE To study whether FIV mediates the relationship between EVT and functional outcome in patients with acute ischemic stroke. DESIGN, SETTING, AND PARTICIPANTS Patient data from 7 randomized multicenter trialswere pooled. These trials were conducted between December 2010 and April 2015 and included 1764 patients randomly assigned to receive either EVT or standard care (control). Follow-up infarct volume was assessed on computed tomography ormagnetic resonance imaging after stroke onset. Mediation analysis was performed to examine the potential causal chain in which FIV may mediate the relationship between EVT and functional outcome. A total of 1690 patients met the inclusion criteria. Twenty-five additional patients were excluded, resulting in a total of 1665 patients, including 821 (49.3%) in the EVT group and 844 (50.7%) in the control group. Data were analyzed from January to June 2017. MAIN OUTCOME AND MEASURE The 90-day functional outcome via the modified Rankin Scale (mRS). RESULTS Among 1665 patients, the median (interquartile range [IQR]) age was 68 (57-76) years, and 781 (46.9%) were female. The median (IQR) time to FIV measurement was 30 (24-237) hours. The median (IQR) FIV was 41 (14-120) mL. Patients in the EVT group had significantly smaller FIVs compared with patients in the control group (median [IQR] FIV, 33 [11-99] vs 51 [18-134] mL; P =.007) and lower mRS scores at 90 days (median [IQR] score, 3 [1-4] vs 4 [2-5]). Follow-up infarct volume was a predictor of functional outcome (adjusted common odds ratio, 0.46; 95% CI, 0.39-0.54; P <.001). Follow-up infarct volume partially mediated the relationship between treatment type with mRS score, as EVT was still significantly associated with functional outcome after adjustment for FIV (adjusted common odds ratio, 2.22; 95% CI, 1.52-3.21; P <.001). Treatment-reduced FIV explained 12%(95% CI, 1-19) of the relationship between EVT and functional outcome. CONCLUSIONS AND RELEVANCE In this analysis, follow-up infarct volume predicted functional outcome; however, a reduced infarct volume after treatment with EVT only explained 12% of the treatment benefit. Follow-up infarct volume as measured on computed tomography and magnetic resonance imaging is not a valid proxy for estimating treatment effect in phase II and III trials of acute ischemic stroke.

引用

页码：194 / 202

页数：9

共 30 条

[1] Posttreatment Infarct Volumes when Compared with 24-Hour and 90-Day Clinical Outcomes: Insights from the REVASCAT Randomized Controlled Trial [J].

Al-Ajlan, F. S. ;

Al Sultan, A. S. ;

Minhas, P. ;

Assis, Z. ;

de Miquel, M. A. ;

Millan, M. ;

San Roman, L. ;

Tomassello, A. ;

Demchuk, A. M. ;

Jovin, T. G. ;

Cuadras, P. ;

Davalos, A. ;

Goyal, M. ;

Menon, B. K. .

AMERICAN JOURNAL OF NEURORADIOLOGY, 2018, 39 (01) :107-110

[2] Intra-Arterial Therapy and Post-Treatment Infarct Volumes Insights From the ESCAPE Randomized Controlled Trial [J].

Al-Ajlan, Fahad S. ;

Goyal, Mayank ;

Demchuk, Andrew M. ;

Minhas, Priyanka ;

Sabiq, Farahna ;

Assis, Zarina ;

Willinsky, Robert ;

Montanera, Walter J. ;

Rempel, Jeremy L. ;

Shuaib, Ashfaq ;

Thornton, John ;

Williams, David ;

Roy, Daniel ;

Poppe, Alexandre Y. ;

Jovin, Tudor G. ;

Sapkota, Biggya L. ;

Baxter, Blaise W. ;

Krings, Timo ;

Silver, Frank L. ;

Frei, Donald F. ;

Fanale, Christopher ;

Tampieri, Donatella ;

Teitelbaum, Jeanne ;

Lum, Cheemun ;

Dowlatshahi, Dar ;

Shankar, Jai J. ;

Barber, Philip A. ;

Hill, Michael D. ;

Menon, Bijoy K. .

STROKE, 2016, 47 (03) :777-781

[3] Relationships Between Imaging Assessments and Outcomes in Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke [J].

Albers, Gregory W. ;

Goyal, Mayank ;

Jahan, Reza ;

Bonafe, Alain ;

Diener, Hans-Christoph ;

Levy, Elad I. ;

Pereira, Vitor M. ;

Cognard, Christophe ;

Yavagal, Dileep R. ;

Saver, Jeffrey L. .

STROKE, 2015, 46 (10) :2786-2794

[4] Selective neuronal loss in ischemic stroke and cerebrovascular disease [J].

Baron, Jean-Claude ;

Yamauchi, Hiroshi ;

Fujioka, Masayuki ;

Endres, Matthias .

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2014, 34 (01) :2-18

[5] THE MODERATOR MEDIATOR VARIABLE DISTINCTION IN SOCIAL PSYCHOLOGICAL-RESEARCH - CONCEPTUAL, STRATEGIC, AND STATISTICAL CONSIDERATIONS [J].

BARON, RM ;

KENNY, DA .

JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY, 1986, 51 (06) :1173-1182

[6] A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke [J].

Berkhemer, O. A. ;

Fransen, P. S. S. ;

Beumer, D. ;

van den Berg, L. A. ;

Lingsma, H. F. ;

Yoo, A. J. ;

Schonewille, W. J. ;

Vos, J. A. ;

Nederkoorn, P. J. ;

Wermer, M. J. H. ;

van Walderveen, M. A. A. ;

Staals, J. ;

Hofmeijer, J. ;

van Oostayen, J. A. ;

Nijeholt, G. J. Lycklama A. ;

Boiten, J. ;

Brouwer, P. A. ;

Emmer, B. J. ;

de Bruijn, S. F. ;

van Dijk, L. C. ;

Kappelle, L. J. ;

Lo, R. H. ;

Van Dijk, E. J. ;

de Vries, J. ;

de Kort, P. L. M. ;

van Rooij, W. J. J. ;

van den Berg, J. S. P. ;

van Hasselt, B. A. A. M. ;

Aerden, L. A. M. ;

Dallinga, R. J. ;

Visser, M. C. ;

Bot, J. C. J. ;

Vroomen, P. C. ;

Eshghi, O. ;

Schreuder, T. H. C. M. L. ;

Heijboer, R. J. J. ;

Keizer, K. ;

Tielbeek, A. V. ;

den Hertog, H. M. ;

Gerrits, D. G. ;

van den Berg-Vos, R. M. ;

Karas, G. B. ;

Steyerberg, E. W. ;

Flach, H. Z. ;

Marquering, H. A. ;

Sprengers, M. E. S. ;

Jenniskens, S. F. M. ;

Beenen, L. F. M. ;

van den Berg, R. ;

Koudstaal, P. J. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (01) :11-20

[7] Automated Cerebral Infarct Volume Measurement in Follow-up Noncontrast CT Scans of Patients with Acute Ischemic Stroke [J].

Boers, A. M. ;

Marquering, H. A. ;

Jochem, J. J. ;

Besselink, N. J. ;

Berkhemer, O. A. ;

van der Lugt, A. ;

Beenen, L. F. ;

Majoie, C. B. .

AMERICAN JOURNAL OF NEURORADIOLOGY, 2013, 34 (08) :1522-1527

[8] Association of follow-up infarct volume with functional outcome in acute ischemic stroke: a pooled analysis of seven randomized trials [J].

Boers, Anna M. M. ;

Jansen, Ivo G. H. ;

Beenen, Ludo F. M. ;

Devlin, Thomas G. ;

San Roman, Luis ;

Heo, Ji Hoe ;

Ribo, Marc ;

Brown, Scott ;

Almekhlafi, Mohammed A. ;

Liebeskind, David S. ;

Teitelbaum, Jeanne ;

Lingsma, Hester F. ;

van Zwam, Wim H. ;

Cuadras, Patricia ;

de Rochemont, Richard du Mesnil ;

Beaumont, Marine ;

Brown, Martin M. ;

Yoo, Albert J. ;

van Oostenbrugge, Robert J. ;

Menon, Bijoy K. ;

Donnan, Geoffrey A. ;

Mas, Jean Louis ;

Roos, Yvo B. W. E. M. ;

Oppenheim, Catherine ;

van der Lugt, Aad ;

Dowling, Richard J. ;

Hill, Michael D. ;

Davalos, Antoni ;

Moulin, Thierry ;

Agrinier, Nelly ;

Demchuk, Andrew M. ;

Lopes, Demetrius K. ;

Aja Rodriguez, Lucia ;

Dippel, Diederik W. J. ;

Campbell, Bruce C. V. ;

Mitchell, Peter J. ;

Al-Ajlan, Fahad S. ;

Jovin, Tudor G. ;

Madigan, Jeremy ;

Albers, Gregory W. ;

Soize, Sebastien ;

Guillemin, Francis ;

Reddy, Vivek K. ;

Bracard, Serge ;

Blasco, Jordi ;

Muir, Keith W. ;

Nogueira, Raul G. ;

White, Phil M. ;

Goyal, Mayank ;

Davis, Stephen M. .

JOURNAL OF NEUROINTERVENTIONAL SURGERY, 2018, 10 (12) :1137-1142

[9] Mechanical thrombectomy after intravenous alteplase versus alteplase alone after stroke (THRACE): a randomised controlled trial [J].

Bracard, Serge ;

Ducrocq, Xavier ;

Mas, Jean Louis ;

Soudant, Marc ;

Oppenheim, Catherine ;

Moulin, Thieriy ;

Guillemin, Francis .

LANCET NEUROLOGY, 2016, 15 (11) :1138-1147

[10] Associations of Ischemic Lesion Volume With Functional Outcome in Patients With Acute Ischemic Stroke 24-Hour Versus 1-Week Imaging [J].

Bucker, Amber ;

Boers, Anna M. ;

Bot, Joseph C. J. ;

Berkhemer, Olvert A. ;

Lingsma, Hester F. ;

Yoo, Albert J. ;

Van Zwam, Wim H. ;

Van Oostenbrugge, Robert J. ;

Van der Lugt, Aad ;

Dippel, Diederik W. J. ;

Roos, Yvo B. W. E. M. ;

Majoie, Charles B. L. M. ;

Marquering, Henk A. .

STROKE, 2017, 48 (05) :1233-+

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