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

Research output: Contribution to journalArticle

Authors

  • Aleksandra Gasecka
  • Rienk Nieuwland
  • Monika Budnik
  • Francoise Dignat-George
  • Ceren Eyileten
  • Romaric Lacroix
  • Aurelie Leroyer
  • Grzegorz Opolski
  • Kinga Pluta
  • Edwin van der Pol
  • Marek Postula
  • Pia Siljander
  • Jolanta M Siller-Matula
  • Krzysztof Filipiak

Colleges, School and Institutes

External organisations

  • Medical University of Warsaw
  • Medical University of Warsaw
  • University of Amsterdam
  • Aix Marseille University
  • Hôpital de la Conception, Assistance Publique Hôpital de Marseille
  • University of Helsinki
  • Medical University of Vienna

Abstract

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+), from leukocytes (CD45+), endothelial cells (CD31+,146+) and erythrocytes (CD235a+) in plasma at randomisation, after 72 hours and 6 months of treatment. 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≤0.03). Concentrations of platelet EVs were lower on ticagrelor compared to clopidogrel after 6 months (p=0.03). Concentrations of fibrinogen+, PS+ and leukocyte EVs were lower on ticagrelor compared to clopidogrel both after 72 hours and 6 months (p≤0.03). Concentrations of endothelial EVs and
20 EV procoagulant activity did not differ between patient groups and over time (p≥0.17).

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.

Details

Original languageEnglish
Pages (from-to)1-15
Number of pages15
JournalJournal of thrombosis and haemostasis : JTH
Early online date12 Dec 2019
Publication statusE-pub ahead of print - 12 Dec 2019

Keywords

  • ADP receptors, antiplatelet drugs, extracellular vesicles, platelets, ticagrelor