Abstract 27: A Novel Adjuvant Strategy After Endovascular Therapy: Arterial Glyceryl Trinitrate in Acute Ischemic Stroke for Neuroprotection (AGAIN)

Abstract

Introduction: Although mechanical thrombectomy (MT) demonstrates robust clinical efficacy in acute ischemic stroke (AIS), not all stroke patients benefit from successful reperfusion. The protective effect of NO donors has been shown to prevent ischemia-reperfusion injury through reduction of reactive oxygen species formation in cardiovascular studies. Glyceryl Trinitrate (GTN), a Food and Drug Administration-approved vasodilator, is one of the widely used exogenous NO donors used in the clinic and has been trialed for neuroprotection in AIS without successful clinical translation. The recent advances in MT for AIS have paved the way for promising new opportunities to supplementary neuroprotective therapies to patients after reperfusion. This study evaluated the safety, feasibility, and preliminary efficacy of intra-arterial administration of GTN after MT for neuroprotection. Methods: This is a prospective randomized controlled study (ID: ChiCTR2100045254). Eligible patients were randomized to receive 800μg GTN or same volume of normal saline through the catheter after recanalization. The primary outcome was symptomatic intracranial hemorrhage (sICH), while secondary outcomes included mortality, functional outcome, infarction volume, complications, and blood nitrate index (NOx). Results: A total of 40 patients were enrolled and randomized with no participants being lost to follow-up. There was no significant difference in the proportion of sICH between GTN and control groups. No significant difference was observed in mortality or rates of neurological deterioration and other complications. Favorable trends for both functional independence (mRS 0-2, 75.0% vs. 65.0%) at 90 days and reduction in final infarct volume (33.2 vs. 38.9 ml) have been observed in GTN group, although they did not reach the significant levels. Moreover, the concentration of blood NO X was increased (p<0.05) at 2 hours after GTN administration (26.2 vs 18.0 μmol/l). Conclusion: The AGAIN study suggests intra-arterial administration of GTN post MT is safe and feasible in AIS patient. The discernible positive trends may be due to the raised NO X levels, which potentially highlight the mechanistic reinforcement for these observed benefits.