Glenzocimab in Anterior Stroke With Large Ischemic Core Eligible for Endovascular Therapy

Until recently, acute ischemic stroke (AIS) patients with a baseline large infarct core have been generally excluded from clinical trials of endovascular therapy (EVT). A first multicenter randomized trial (Rescue Japan Limit trial) found a significant benefit of EVT in AIS patients with large infarct core (DWI-ASPECTS of 3-5). Another non-randomized multicenter prospective study found a positive association of EVT with 3-month outcome in AIS patients with a baseline CTP ischemic core volume \>70mL. More recently, 2 additional randomized trials were published. They both confirmed a strong efficacy of EVT in patients with large infarct core. However, even with EVT, the proportion of good outcome (3-month mRS score of 0-3), remains low in these highly severe AIS patients ranging from 8-30%. Almost 75% of EVT-treated patients are still severely disabled or dead at 3 months. In experimental studies, we and others described the pathophysiological features of the downstream microvascular thrombosis (DMT) in AIS setting highlighting its immediate occurrence and the pivotal role of platelet activation and aggregation. In recent clinical studies, it has been shown that, even with a complete angiographic recanalization after EVT, up to 40% of patients presented no-reflow (NR), a failure of downstream microvascular reperfusion, visible on perfusion imaging performed after EVT. Some clinical studies reported the clinical impact of NR after successful EVT. We found that DMT participated to the development of neurovascular lesions in AIS with both an early ischemic lesion growth risk evolving towards a delayed hemorrhagic transformation (HT) and vasogenic edema risks and therefore worse outcome. Our results suggested that an antiplatelet therapy infused early in AIS patients could reduce both the ischemic lesion but also the risk of delayed vasogenic edema and HT. Platelet glycoprotein VI (GPVI) is a key receptor for collagen and fibrin and plays a major role in platelet activati