TY - JOUR
T1 - Ticagrelor attenuates the increase of extracellular vesicle concentrations in plasma after acute myocardial infarction compared to clopidogrel
AU - Gasecka, Aleksandra
AU - Nieuwland, Rienk
AU - Budnik, Monika
AU - Dignat-George, Françoise
AU - Eyileten, Ceren
AU - Harrison, Paul
AU - Lacroix, Romaric
AU - Leroyer, Aurélie
AU - Opolski, Grzegorz
AU - Pluta, Kinga
AU - van der Pol, Edwin
AU - Postuła, Marek
AU - Siljander, Pia
AU - Siller-Matula, Jolanta M.
AU - Filipiak, Krzysztof J.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - 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.
AB - 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.
KW - adenosine diphosphate receptors
KW - antiplatelet drugs
KW - extracellular vesicles
KW - platelets
KW - ticagrelor
UR - http://www.scopus.com/inward/record.url?scp=85077908463&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/jth.14689
DO - https://doi.org/10.1111/jth.14689
M3 - Article
C2 - 31833175
SN - 1538-7933
VL - 18
SP - 609
EP - 623
JO - Journal of thrombosis and haemostasis
JF - Journal of thrombosis and haemostasis
IS - 3
ER -