Randomized controlled trial protocol to investigate the antiplatelet therapy effect on extracellular vesicles in acute myocardial infarction (AFFECT EV)

Aleksandra Gasecka, Rienk Nieuwland, Monika Budnick, Francoise Dignat-George, Ceren Eyileten, Paul Harrison, Zenon Huczek, Agnieszka Kaplon-Cieslicka, Romaric Lacroix, Grzegorz Opolski, Kinga Pluta, Edwin van der Pol, Marek Postula, Aurelie Leroyer, Pia Siljander, Auguste Starke, Krzysztof Filipiak

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Abstract

Activated platelets contribute to thrombosis and inflammation by the release of extracellular 2 vesicles (EVs) exposing P-selectin, phosphatidylserine (PS) and fibrinogen. P2Y12 receptor 3 antagonists are routinely administered to inhibit platelet activation in patients after acute 4 myocardial infarction (AMI), being a combined anti-thrombotic and anti-inflammatory 5 therapy. The more potent P2Y12 antagonist ticagrelor improves cardiovascular outcome in 6 patients after AMI compared to the less potent clopidogrel, suggesting that greater inhibition 7 of platelet aggregation (IPA) is associated with better prognosis. The effect of ticagrelor and 8 clopidogrel on the release of EVs from platelets and other P2Y12-exposing cells is unknown. 9 This study compares the effects of ticagrelor and clopidogrel on (i) the concentrations of EVs 10 from activated platelets (primary end-point), (ii) the concentrations of EVs exposing 11 fibrinogen, exposing PS, from leukocytes and from endothelial cells (secondary end-points) 12 and (iii) the procoagulant activity of plasma EVs (tertiary end-points) in 60 consecutive AMI 13 patients. After the percutaneous coronary intervention, patients will be randomized to 14 antiplatelet therapy with ticagrelor (study group) or clopidogrel (control group). Blood will be 15 collected from patients at randomisation, 48 hours after randomisation, and 6 months 16 following the index hospitalization. In addition, 30 age- and gender-matched healthy 17 volunteers will be enrolled in the study to investigate the physiological concentrations and 18 procoagulant activity of EVs using recently standardized protocols and EV-dedicated flow 19 cytometry. Concentrations of EVs will be determined by flow cytometry. Procoagulant 20 activity of EVs will be determined by fibrin generation test. The compliance and response to 21 antiplatelet therapy will be assessed by impedance aggregometry. We expect that plasma from 22 patients treated with ticagrelor (i) contains lower concentrations of EVs from activated 23 platelets, exposing fibrinogen, exposing PS, from leukocytes and from endothelial cells, and 24 (ii) has lower procoagulant activity, when compared to patients treated with clopidogrel. 25
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AFFECT EV may identify a new mechanism of action of ticagrelor, as well as create a basis 1 for future studies to investigate whether lower EV concentrations are associated with 2 improved clinical outcomes in patients treated with P2Y12 antagonists.
Original languageEnglish
Number of pages23
JournalPlatelets
Early online date26 Dec 2018
DOIs
Publication statusE-pub ahead of print - 26 Dec 2018

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