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

被引：53

作者：

Gasecka, Aleksandra ^{[1
,2
,3
]}

Nieuwland, Rienk ^{[2
,3
]}

Budnik, Monika ^{[1
]}

Dignat-George, Francoise ^{[4
,5
]}

Eyileten, Ceren ^{[6
]}

Harrison, Paul ^{[7
]}

Lacroix, Romaric ^{[4
,5
]}

Leroyer, Aurelie ^{[4
]}

Opolski, Grzegorz ^{[1
]}

Pluta, Kinga ^{[1
]}

van der Pol, Edwin ^{[2
,3
,8
]}

Postula, Marek ^{[6
]}

Siljander, Pia ^{[9
]}

Siller-Matula, Jolanta M. ^{[10
]}

Filipiak, Krzysztof J. ^{[1
]}

机构：

[1] Med Univ Warsaw, Chair & Dept Cardiol 1, Warsaw, Poland

[2] Univ Amsterdam, Amsterdam UMC, Vesicle Observat Ctr, Amsterdam, Netherlands

[3] Univ Amsterdam, Amsterdam UMC, Lab Expt Clin Chem, Amsterdam, Netherlands

[4] Aix Marseille Univ, Fac Pharm, INSERM, Marseille, France

[5] CHU Conception, AP HM, Hematol & Vasc Biol Dept, Marseille, France

[6] Med Univ Warsaw, Ctr Preclin Res & Technol, Dept Expt & Clin Pharmacol, Warsaw, Poland

[7] Univ Birmingham, Inst Inflammat & Ageing, Birmingham, W Midlands, England

[8] Univ Amsterdam, Amsterdam UMC, Biomed Engn & Phys, Amsterdam, Netherlands

[9] Univ Helsinki, Fac Biol & Environm Sci, Mol & Integrat Biosci Res Programme, EV Grp, Helsinki, Finland

[10] Med Univ Vienna, Dept Cardiol, Vienna, Austria

来源：

JOURNAL OF THROMBOSIS AND HAEMOSTASIS | 2020年 / 18卷 / 03期

关键词：

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;

D O I：

10.1111/jth.14689

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：609 / 623

页数：15

共 50 条

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