Ticagrelor attenuates the increase of extracellular vesicle concentrations in plasma after acute myocardial infarction compared to clopidogrel

Aleksandra Gasecka (1) , Rienk Nieuwland (1) , Monika Budnik (2) , Francoise Dignat-George (3, 4) , Ceren Eyileten (2) , Paul Harrison (5) , Romaric Lacroix (3, 4) , Aurélie Leroyer (3) , Grzegorz Opolski (2) , Kinga Pluta (2) , Edwin Pol (1) , Marek Postuła (2) , Pia Siljander (6) , Jolanta Siller‐matula (7) , Krzysztof Filipiak (2)

1 UvA - University of Amsterdam [Amsterdam] = Universiteit van Amsterdam
2 Medical University of Warsaw - Poland
3 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
4 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]
5 University of Birmingham [Birmingham]
6 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
7 Medizinische Universität Wien = Medical University of Vienna

Background Platelet P2Y12 antagonist ticagrelor reduces mortality after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets, leukocytes, and endothelial cells release proinflammatory and prothrombotic extracellular vesicles (EVs), we hypothesized that the release of EVs is more efficiently inhibited by ticagrelor compared to clopidogrel. Objectives We compared EV concentrations and EV procoagulant activity in plasma of patients after AMI treated with ticagrelor or clopidogrel. Methods After percutaneous coronary intervention, 60 patients with first AMI were randomized to ticagrelor or clopidogrel. Flow cytometry was used to determine concentrations of EVs from activated platelets (CD61(+), CD62p(+)), fibrinogen(+), phosphatidylserine (PS+), leukocytes (CD45(+)), endothelial cells (CD31(+), 146(+)), and erythrocytes (CD235a(+)) in plasma at randomization, after 72 hours and 6 months of treatment. A fibrin generation test was used to determine EV procoagulant activity. Results Concentrations of platelet, fibrinogen(+), PS+, leukocyte, and erythrocyte EVs increased 6 months after AMI compared to the acute phase of AMI (P <= .03). Concentrations of platelet EVs were lower on ticagrelor compared to clopidogrel after 6 months (P = .03). Concentrations of fibrinogen(+), PS+, and leukocyte EVs were lower on ticagrelor compared to clopidogrel both after 72 hours and 6 months (P <= .03). Concentrations of endothelial EVs and EV procoagulant activity did not differ between patient groups and over time (P >= .17). Conclusions Ticagrelor attenuates the increase of EV concentrations in plasma after acute myocardial infarction compared to clopidogrel. The ongoing release of EVs despite antiplatelet therapy might explain recurrent thrombotic events after AMI and worse clinical outcomes on clopidogrel compared to ticagrelor.

Mots clés: adenosine diphosphate receptors; antiplatelet drugs; extracellular vesicles; platelets; ticagrelor; PLATELET-DERIVED MICROPARTICLES; P2Y(12) RECEPTOR ANTAGONISTS; ANTIPLATELET THERAPY; PROCOAGULANT ACTIVITY; 2017 ESC; ADENOSINE; THROMBOSIS; BLOOD; MICROVESICLES; AGGREGATION

Domaines: Sciences du Vivant [q-bio]; Médecine humaine et pathologie; Hématologie

Aleksandra Gasecka, Rienk Nieuwland, Monika Budnik, Francoise Dignat-George, Ceren Eyileten, et al.. Ticagrelor attenuates the increase of extracellular vesicle concentrations in plasma after acute myocardial infarction compared to clopidogrel. Journal of Thrombosis and Haemostasis, 2020, 18 (3), pp.609-623. ⟨10.1111/jth.14689⟩. ⟨hal-03176804⟩