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JAMA Neurol. 2019 Feb 1;76(2):194-202. doi: 10.1001/jamaneurol.2018.3661.

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

Author information

1
Department of Biomedical Engineering and Physics, Amsterdam University Medical Center, location AMC, Amsterdam, the Netherlands.
2
Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, location AMC, Amsterdam, the Netherlands.
3
Department of Robotics and Mechatronics, University of Twente, Enschede, the Netherlands.
4
Altair Biostatistics, Mooresville, North Carolina.
5
Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands.
6
Department of Neurology, Erlanger Hospital, University of Tennessee at Chattanooga.
7
Department of Interventional Neuroradiology, Hospital Clinic of Barcelona, Barcelona, Catalonia, Spain.
8
Department of Neurology, Yonsei University, Seoul, South Korea.
9
Department of Neurology, Vall d'Hebron University Hospital, Barcelona, Catalonia, Spain.
10
Department of Neurology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
11
Department of Neurology, University of California, Los Angeles.
12
Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
13
Department of Radiology, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
14
Department of Radiology, Goethe University Hospital, University of Frankfurt, Frankfurt, Germany.
15
Inserm CIC-IT 1433, University of Lorraine and University Hospital of Nancy, Nancy, France.
16
Institute of Neurology, University College London, London, United Kingdom.
17
Division of Neurointervention, Texas Stroke Institute, Dallas.
18
The Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.
19
Department of Neurology, Sainte-Anne Hospital and Paris-Descartes University, INSERM U894, Paris, France.
20
Department of Neuroradiology, Sainte-Anne Hospital and Paris-Descartes University, INSERM U894, Paris, France.
21
Department of Radiology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.
22
Department of Neurology, University Hospital of Besançon, University of Franche-Comté, Besançon, France.
23
Inserm, Centre Hospitalier Régional et Universitaire de Nancy, Université de Lorraine, CIC1433-Epidémiologie Clinique, Nancy, France.
24
Department of Neurological Surgery, Rush University Medical Center, Chicago, Illinois.
25
Neuroradiology Department, Hospital Universitari de Bellvitge, Barcelona, Catalonia, Spain.
26
Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
27
Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands.
28
Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
29
St George's University Hospital, London, United Kingdom.
30
Department of Neurology, Stanford Stroke Center, Palo Alto, California.
31
Department of Neuroradiology, University Hospital of Reims, Reims, France.
32
Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.
33
Department of Neurology, Neurosurgery and Radiology, Grady Memorial Hospital, Emory University School of Medicine, Atlanta, Georgia.
34
Department of Neuroscience, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
35
Department of Clinical Neurosciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Foothills Hospital, Calgary, Alberta, Canada.
36
Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, United Kingdom.
37
Department of Neurology, Amsterdam University Medical Center, location AMC, Amsterdam, the Netherlands.
38
Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
39
Department of Radiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center+, Maastricht, the Netherlands.
40
Stroke Institute, Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
41
Department of Neurology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center+, Maastricht, the Netherlands.
42
Department of Diagnostic and Interventional Neuroradiology, INSERM U947, University of Lorraine and University Hospital of Nancy, Nancy, France.

Abstract

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 trials were 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 or magnetic 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.

PMID:
30615038
PMCID:
PMC6439953
[Available on 2020-01-07]
DOI:
10.1001/jamaneurol.2018.3661

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