Comparison of NIHSS Within 7-day and 90-day mRS Outcomes in Randomized-controlled Trials of Acute Ischemic Stroke: A Systematic Review and Meta-analysis
Leon Rinkel1, Johanna Ospel1, Manon Kappelhof2, Arshia Sehgal1, Rosalie McDonough1, Michael Tymianski3, Michael Hill1, Mayank Goyal1, Aravind Ganesh1
1Foothills Medical Center, University of Calgary, 2University Medical Centers Amsterdam, location University of Amsterdam, 3NoNO, Toronto, ON, Canada
Objective:

To evaluate agreement between National Institutes of Health Stroke Scale (NIHSS) assessed within 7-days follow-up and 90-day modified Rankin Scale (mRS) outcomes in randomized-controlled trials (RCTs).

Background:

Since factors independent of acute ischemic stroke (AIS) can confound 90-day outcomes in RCTs of acute treatments, early NIHSS may be a suitable alternative.

Design/Methods:

We conducted a meta-analysis including RCTs of acute therapies for AIS published until 01-April-2023, with available data for both 90-day mRS and NIHSS within 7-days. Primary outcome was agreement between trial results (classified as positive versus negative/neutral) based on 24-hour NIHSS and 90-day mRS. We additionally assessed agreement for 2-hours, 48-hours, 72-hours, 4-days, 5-days, 6-days and 7-days NIHSS. We aimed to validate our study-level findings using individual patient data from the ESCAPE and ESCAPE-NA1 RCTs, comparing NIHSS at 2-hours, 24-hours, 48-hours, and 5-7 days with 90-day mRS (both dichotomized at 0-2).

Results:

We included 116 trials (44,387 patients, median age 68 [IQR 66-72] years, 25,218 [56.8%] men), contributing 170 NIHSS assessments performed across the 8 timepoints. For 24-hour NIHSS, there was agreement with 90-day mRS assessments in 63/74 (85%) trials. Agreement varied numerically by timing of NIHSS assessments, ranging from 80%–100%, but differences were not statistically significant (p=0.76). Whereas ESCAPE and ESCAPE-NA1 data showed agreement in overall trial results for all timepoints except 2-hour NIHSS, agreement with 90-day mRS for individual patient outcomes was lower (3523/5195, 67.8%) but improved with later assessments (2-hours: 56.6%; 24-hours: 66.6%; 48-hours: 72.7%; 5-7 days: 76.5%,p<0.01).

Conclusions:

NIHSS assessed between 24-hours and 7-days follow-up results in similar overall conclusions as 90-day mRS in identifying positive versus neutral/negative RCTs, indicating its value as an alternative primary outcome measure for AIS treatments. However, individual patient level data showed that NIHSS within 7-days risks misclassifying 1 in 3 patients with respect to 90-day mRS, although agreement improves with later assessments.

10.1212/WNL.0000000000205695