GPVI inhibition by glenzocimab synergistically inhibits atherosclerotic plaque-induced platelet activation when combined with conventional dual antiplatelet therapy
نویسندگان
چکیده
Abstract Introduction Aspirin and a potent platelet P2Y12 inhibitor, such as prasugrel or ticagrelor, are not always sufficient to prevent thrombus formation in patients with ST-elevation MI (STEMI), leading “slow flow” “no reflow” effects after stenting. GPIIb/IIIa inhibitors, eptifibatide, may help this setting, but used routinely due their bleeding risk. GPVI has critical roles thrombosis minimal role haemostasis. Here we tested whether depletion of on an animal model investigated the novel glenzocimab (a Fab fragment monoclonal antibody), activation when combined aspirin ticagrelor. Methods We intravital microscopy murine myocardial infarction ischaemia-reperfusion injury investigate microvascular thrombosis. antithrombotic adding (previously known ACT017) blood from healthy donors 20 ACS treated compared effect inhibitor eptifibatide ex-vivo. stimulated platelets collagen atherosclerotic plaque material that was sourced undergoing carotid endarterectomy. aggregation, spreading, signalling, adhesion, thrombin generation, clot stability ex vivo. Results Genetic reduced Ex vivo, ticagrelor partially inhibited plaque-induced aggregation (assessed by multiple electrode aggregometry) 48% control (34±3 vs. 65±4 U; P<0.001; Figure 1). Atherosclerotic secretion were critically dependent potently glenzocimab. Glenzocimab alone 75% (16±4 1) over 95% (3±1 vs Furthermore, provided synergistic added ticagrelor-treated had many similar less mechanisms general haemostasis assessed ROTEM (Figure 2). Conclusions The addition provides inhibition atherothrombosis. share effects, although impact involved eptifibatide. Funding Acknowledgement Type funding sources: Public grant(s) – National budget only. Main source(s): Academy Medical Sciences UK Clinical Lecturer Starter GrantRoyal Embassy Saudi Arabia
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ژورنال
عنوان ژورنال: European Heart Journal
سال: 2021
ISSN: ['2634-3916']
DOI: https://doi.org/10.1093/eurheartj/ehab724.1425