Advances in Acute Stroke Treatment 2020

Joseph P. Broderick, MD; Michael D. Hill, MD, MSc, FRCPC


Stroke. 2021;52(2):729-734. 

Cytoprotection and Adjuvant Therapies for Ischemic Stroke Reperfusion

The evolution of treatments for ischemic stroke due to LVO has resulted in a true human ischemia-reperfusion model, the same model in which preclinical demonstration of cytoprotection (or neuroprotection) has been proven for multiple compounds. The ESCAPE-NA1 trial (Extension of Stroke Care by Added neuroProtection to Endovascular treatment) assessed the peptide, nerinetide (previously called NA-1, TatNR2b9c), among 1105 patients with anterior circulation LVO undergoing EVT.[22] The trial stratified randomization by alteplase treatment but was neutral overall. However, there was an alteplase-by-nerinetide treatment interaction, such that patients in the alteplase stratum showed no benefit, but patients in the no-alteplase stratum showed a 9.5% absolute risk benefit (risk ratio, 1.19 [95% CI, 1.01–1.41]). This was a post hoc test of interaction but was biologically supported by pharmacokinetic studies which suggest that there was an indirect effect of alteplase on cleavage of nerinetide in vivo. If the results can be confirmed in the ESCAPE-NEXT trial (Efficacy and Safety of Nerinetide in Participants With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy Excluding Thrombolysis), this will give hope to other compounds that are being developed using the same paradigm. These include the modified activated protein C molecule, 3K3A-APC, which has already undergone assessment in the phase 2 Rhapsody study.[23] Simple molecules such as high-dose uric acid[24,25] may be assessed in future trials.