Abstract WP106: Redefined Measure of Early Neurological Improvement Shows Treatment Benefit of Intravenous Tissue Plasminogen Activator Treatment in NINDS Rt-PA Acute Stroke Trial at 24 Hours

Abstract

Background and Purpose: The first of the 2 NINDS Stroke Study trials did not show a significant increase in early neurological improvement (ENI), defined as NIHSS improvement by ≥ 4, with alteplase treatment. We hypothesized that ENI defined as a percentage change in NIHSS (percent change NIHSS) at 24 hours is superior to other definitions in predicting 3-month functional outcomes and using this definition there would be treatment benefit of alteplase over placebo at 24 hours. Methods: We analyzed the NINDS rt-PA Stroke Study (Parts 1 and 2) trial data. Percent change NIHSS was defined as [(admission NIHSS score–24-hour NIHSS score)x100/admission NIHSS score] and delta NIHSS as (admission NIHSS score–24-hour NIHSS score). We compared ENI using these definitions between alteplase vs. placebo patients. We also used receiver operating characteristic (ROC) curve to determine the predictive association of ENI with excellent 3-month functional outcomes [Barthel Index (BI) score 95 – 100 and modified Rankin scale (mRS) 0-1], good 3-month functional outcome (mRS 0-2) and 3-month infarct volume. Results: There was a significantly greater improvement in the 24-hour median percent change NIHSS among patients treated with alteplase compared to the placebo group (28% vs. 15%, p = 0.045) but not median delta NIHSS (3 vs. 2, p = 0.471). ROC curve comparison showed that percent change NIHSS (ROC percent ) was better than delta NIHSS (ROC delta ) and admission NIHSS (ROC admission ) with regards to excellent 3-month BI (ROC percent 0.83, ROC delta 0.76, ROS admission 0.75), excellent 3-month mRS (ROC percent 0.83, ROC delta 0.74, ROS admission 0.78), and good 3-month mRS (ROC percent 0.83, ROC delta 0.76, ROS admission 0.78). Percentage change had a stronger association with 90-day infarct volume than delta NIHSS score and both delta NIHSS and percent change in NIHSS were more pronounced with faster treatment times. Conclusion: In the NINDS rt-PA trial, alteplase was associated with a significant percent change improvement in NIHSS at 24 hours. Percent change in NIHSS may be a better surrogate marker of thrombolytic activity and 3-month outcomes.