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 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-togood 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.