Comparing Early National Institutes of Health Stroke Scale Versus 90‐Day Modified Rankin Scale Outcomes in Acute Ischemic Stroke Trials: A Systematic Review and Analysis

Background Early National Institutes of Health Stroke Scale (NIHSS) assessment may provide practical benefits over 90‐day modified Rankin Scale (mRS), but it is unclear how it compares in adjudicating randomized clinical trial (RCT) results in acute ischemic stroke. Methods and Results We searched O...

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Main Authors: Leon A. Rinkel, Johanna M. Ospel, Manon Kappelhof, Arshia Sehgal, Rosalie V. McDonough, Michael Tymianski, Michael D. Hill, Mayank Goyal, Aravind Ganesh
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.124.040304
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author Leon A. Rinkel
Johanna M. Ospel
Manon Kappelhof
Arshia Sehgal
Rosalie V. McDonough
Michael Tymianski
Michael D. Hill
Mayank Goyal
Aravind Ganesh
author_facet Leon A. Rinkel
Johanna M. Ospel
Manon Kappelhof
Arshia Sehgal
Rosalie V. McDonough
Michael Tymianski
Michael D. Hill
Mayank Goyal
Aravind Ganesh
author_sort Leon A. Rinkel
collection DOAJ
description Background Early National Institutes of Health Stroke Scale (NIHSS) assessment may provide practical benefits over 90‐day modified Rankin Scale (mRS), but it is unclear how it compares in adjudicating randomized clinical trial (RCT) results in acute ischemic stroke. Methods and Results We searched Ovid Medline (inception to April 1, 2023) and included RCTs of acute therapies for acute ischemic stroke with data for both 90‐day mRS and NIHSS within 7 days. Primary outcome was agreement between trial results (classified as positive, negative, or neutral) based on 24‐hour NIHSS and 90‐day mRS scores. We additionally assessed agreement for 2‐hour, 48‐hour, 72‐ to 96‐hour, and 5‐ to 7‐day NIHSS scores. We aimed to validate our findings using individual patient data from the ESCAPE (Randomized Assessment of Rapid Endovascular Treatment of Ischemic Stroke) and ESCAPE‐NA1 (Safety and Efficacy of Nerinetide [NA‐1] in Subjects Undergoing Endovascular Thrombectomy for Stroke) RCTs. We included 116 trials (44 387 patients), contributing 165 NIHSS assessments. The 24‐hour NIHSS scores resulted in the same classification as 90‐day mRS scores in 61/73 (83.6%) trials (Cohen's kappa, 0.64 [95% CI: 0.45–0.83] and Gwet's agreement coefficient 1, 0.79 [95% CI: 0.67–0.90]). Agreement was not statistically different by timing of NIHSS assessments (range 75%–100%, P=0.33). Individual patient data showed higher agreement for assessments between 48 hours and 7 days, varying by NIHSS dichotomization cutoffs (NIHSS score, 0–2; 2 hours, 56.6%; 24 hours, 66.6%; 48 hours, 71.8%; 5–7 days: 76.5%, P<0.01; NIHSS score, 0–7; 2 hours, 72.8%; 24 hours, 80.5%; 48 hours, 83.1%; 5–7 days: 84.7%, P<0.01). Conclusions The 24‐hour NIHSS scores aligned with 90‐day mRS scores in 84% of RCT results, indicating intermediate‐to‐good agreement. However, individual patient data showed that early NIHSS risks misclassifying around 1/4 patients. These data contribute to a better understanding of the nuances of early NIHSS score as an outcome in acute ischemic stroke RCTs.
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spelling doaj-art-746c92f306e041ef825a4ed6517ee4772025-08-20T03:07:44ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-05-0114910.1161/JAHA.124.040304Comparing Early National Institutes of Health Stroke Scale Versus 90‐Day Modified Rankin Scale Outcomes in Acute Ischemic Stroke Trials: A Systematic Review and AnalysisLeon A. Rinkel0Johanna M. Ospel1Manon Kappelhof2Arshia Sehgal3Rosalie V. McDonough4Michael Tymianski5Michael D. Hill6Mayank Goyal7Aravind Ganesh8Calgary Stroke Program, Departments of Clinical Neurosciences and Community Health Sciences, The Hotchkiss Brain Institute and the O’Brien Institute for Public Health University of Calgary CanadaCalgary Stroke Program, Departments of Clinical Neurosciences and Community Health Sciences, The Hotchkiss Brain Institute and the O’Brien Institute for Public Health University of Calgary CanadaCalgary Stroke Program, Departments of Clinical Neurosciences and Community Health Sciences, The Hotchkiss Brain Institute and the O’Brien Institute for Public Health University of Calgary CanadaCalgary Stroke Program, Departments of Clinical Neurosciences and Community Health Sciences, The Hotchkiss Brain Institute and the O’Brien Institute for Public Health University of Calgary CanadaCalgary Stroke Program, Departments of Clinical Neurosciences and Community Health Sciences, The Hotchkiss Brain Institute and the O’Brien Institute for Public Health University of Calgary CanadaNoNO Inc. Toronto CanadaCalgary Stroke Program, Departments of Clinical Neurosciences and Community Health Sciences, The Hotchkiss Brain Institute and the O’Brien Institute for Public Health University of Calgary CanadaCalgary Stroke Program, Departments of Clinical Neurosciences and Community Health Sciences, The Hotchkiss Brain Institute and the O’Brien Institute for Public Health University of Calgary CanadaCalgary Stroke Program, Departments of Clinical Neurosciences and Community Health Sciences, The Hotchkiss Brain Institute and the O’Brien Institute for Public Health University of Calgary CanadaBackground Early National Institutes of Health Stroke Scale (NIHSS) assessment may provide practical benefits over 90‐day modified Rankin Scale (mRS), but it is unclear how it compares in adjudicating randomized clinical trial (RCT) results in acute ischemic stroke. Methods and Results We searched Ovid Medline (inception to April 1, 2023) and included RCTs of acute therapies for acute ischemic stroke with data for both 90‐day mRS and NIHSS within 7 days. Primary outcome was agreement between trial results (classified as positive, negative, or neutral) based on 24‐hour NIHSS and 90‐day mRS scores. We additionally assessed agreement for 2‐hour, 48‐hour, 72‐ to 96‐hour, and 5‐ to 7‐day NIHSS scores. We aimed to validate our findings using individual patient data from the ESCAPE (Randomized Assessment of Rapid Endovascular Treatment of Ischemic Stroke) and ESCAPE‐NA1 (Safety and Efficacy of Nerinetide [NA‐1] in Subjects Undergoing Endovascular Thrombectomy for Stroke) RCTs. We included 116 trials (44 387 patients), contributing 165 NIHSS assessments. The 24‐hour NIHSS scores resulted in the same classification as 90‐day mRS scores in 61/73 (83.6%) trials (Cohen's kappa, 0.64 [95% CI: 0.45–0.83] and Gwet's agreement coefficient 1, 0.79 [95% CI: 0.67–0.90]). Agreement was not statistically different by timing of NIHSS assessments (range 75%–100%, P=0.33). Individual patient data showed higher agreement for assessments between 48 hours and 7 days, varying by NIHSS dichotomization cutoffs (NIHSS score, 0–2; 2 hours, 56.6%; 24 hours, 66.6%; 48 hours, 71.8%; 5–7 days: 76.5%, P<0.01; NIHSS score, 0–7; 2 hours, 72.8%; 24 hours, 80.5%; 48 hours, 83.1%; 5–7 days: 84.7%, P<0.01). Conclusions The 24‐hour NIHSS scores aligned with 90‐day mRS scores in 84% of RCT results, indicating intermediate‐to‐good agreement. However, individual patient data showed that early NIHSS risks misclassifying around 1/4 patients. These data contribute to a better understanding of the nuances of early NIHSS score as an outcome in acute ischemic stroke RCTs.https://www.ahajournals.org/doi/10.1161/JAHA.124.040304acute ischemic strokemodified Rankin ScaleNational Institutes of Health Stroke Scalerandomized controlled trial
spellingShingle Leon A. Rinkel
Johanna M. Ospel
Manon Kappelhof
Arshia Sehgal
Rosalie V. McDonough
Michael Tymianski
Michael D. Hill
Mayank Goyal
Aravind Ganesh
Comparing Early National Institutes of Health Stroke Scale Versus 90‐Day Modified Rankin Scale Outcomes in Acute Ischemic Stroke Trials: A Systematic Review and Analysis
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
acute ischemic stroke
modified Rankin Scale
National Institutes of Health Stroke Scale
randomized controlled trial
title Comparing Early National Institutes of Health Stroke Scale Versus 90‐Day Modified Rankin Scale Outcomes in Acute Ischemic Stroke Trials: A Systematic Review and Analysis
title_full Comparing Early National Institutes of Health Stroke Scale Versus 90‐Day Modified Rankin Scale Outcomes in Acute Ischemic Stroke Trials: A Systematic Review and Analysis
title_fullStr Comparing Early National Institutes of Health Stroke Scale Versus 90‐Day Modified Rankin Scale Outcomes in Acute Ischemic Stroke Trials: A Systematic Review and Analysis
title_full_unstemmed Comparing Early National Institutes of Health Stroke Scale Versus 90‐Day Modified Rankin Scale Outcomes in Acute Ischemic Stroke Trials: A Systematic Review and Analysis
title_short Comparing Early National Institutes of Health Stroke Scale Versus 90‐Day Modified Rankin Scale Outcomes in Acute Ischemic Stroke Trials: A Systematic Review and Analysis
title_sort comparing early national institutes of health stroke scale versus 90 day modified rankin scale outcomes in acute ischemic stroke trials a systematic review and analysis
topic acute ischemic stroke
modified Rankin Scale
National Institutes of Health Stroke Scale
randomized controlled trial
url https://www.ahajournals.org/doi/10.1161/JAHA.124.040304
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