For otherwise eligible patients with mild non-disabling stroke symptoms (NIHSS 0 5), IV alteplase is not recommended for patients who could be treated within 3 and 4.5 hours of ischemic stroke symptom onset or patient last known well or at baseline state. III: No Benefit C-LD New recommendation. Subgroup analyses of the NINDS rt-PA Trial and IST (International Stroke Trial)-3 with mild stroke defined in various ways have inconsistently shown a benefit for IV alteplase.161 163 A meta-analysis of 9 trials of IV alteplase in AIS including subjects from the NINDS rt-PA trial and IST-3 showed benefit for patients with mild stroke defined as NIHSS In ECASS III, there was no significant interaction of benefit (mRS score 0 1 at 90 days) or safety (sICH or death) with stroke severity when patients were categorized by baseline NIHSS score of 0 to 9, 10 to 19, and In SITS-ISTR (Safe Implementation of Treatments in Stroke International Stroke Thrombolysis Registry), good functional outcomes (mRS score 0 1 at 90 days) and risk of sICH were similar or the same in mild stroke treated in Similarly, in the AHA GWTG registry, good functional outcomes, mortality, and risk of sICH were the same in mild stroke treated in 0 to 3 and 3 to 4.5 hours.167 These patients were not further categorized by whether their acute neurological deficits were disabling. The PRISMS RCT (A Study of the Safety and Efficacy of Activase [Alteplase] in Patients With Mild Stroke) evaluated IV alteplase in patients with mild (NIHSS score 0 5) AIS whose acute neurological deficits were judged to not interfere with activities of daily living or prevent return to work. There was no benefit of treatment within 3 hours of onset.168 See Tables XXXV and XXXVI in online Data Supplement 1. 3.5.2. 