Abstract
Aims: In this pre-specified analysis of the “endothelium, stent and antiplatelet therapy” study, we investigate the impact of antiplatelet therapies on microvascular function in patients undergoing stenting for an acute coronary syndrome.Methods and Results: Fifty-six patients [age: 63(55–67) years, males, 10 diabetics, 27 non-ST-elevation myocardial infarction] were randomized to receive clopidogrel, ticagrelor or prasugrel in form of oral loading 2 h before stenting followed by oral therapy. Investigators were blinded to the allocation. Laser-Doppler microvascular function and ADP-induced platelet aggregation capacity were measured at baseline, 2 h after oral antiplatelet loading, and 1 day, 1 week and 1 month after stenting during chronic therapy with the same antiplatelet agent. Platelet aggregation decreased in all groups 2 h after oral loading, with a significantly larger effect in the prasugrel group (P = 0.009). Similarly, prasugrel and ticagrelor loading was followed by an increase in microvascular reactive hyperemia (P = 0.007 and P = 0.042 compared to clopidogrel). This effect disappeared one day after coronary intervention, with a significant decrease in the prasugrel group (P = 0.026). Similarly, analysis of microvascular conductance showed a larger increase in the prasugrel group 2 h after loading (P = 0.022 among groups), and a decrease in all groups after stenting.Conclusions: Oral loading with prasugrel (and less consistently ticagrelor) is associated with improved microvascular function and stronger platelet inhibition in acute coronary syndrome patients. The microvascular effect was however lost 1 day after stenting and during subsequent follow-up. Further studies are necessary to clarify the the long-term effects and potential benefits of P2Y12 inhibitors on microvascular damage.ClINICALTRIALS.gov N°: NCT01700322EUDRACT-N°: 2011-005305-73.
Highlights
Platelet activation is associated with the release of mediators of inflammation and oxidative stress, which stimulate leukocyte chemotaxis, aggregation and endothelial dysfunction [reviewed in [1]], impairing micro- and macrovascular function
1 Zentrum für Kardiologie, Kardiologie I, Universitätsmedizin Mainz, Johannes Gutenberg-University Mainz, Mainz, Germany, 2 Center for Thrombosis and Hemostasis, Universitätsmedizin Mainz, Johannes Gutenberg- University Mainz, Mainz, Germany, 3 Institute of Clinical Chemistry and Laboratory Medicine, Universitätsmedizin Mainz, Johannes GutenbergUniversity Mainz, Mainz, Germany, 4 Deutsches Zentrum für Herz Kreislauf-Forschung (DZHK), Standort Rhein-Main, Partnereinrichtung Mainz, Mainz, Germany. In this pre-specified analysis of the “endothelium, stent and antiplatelet therapy” study, we investigate the impact of antiplatelet therapies on microvascular function in patients undergoing stenting for an acute coronary syndrome
Laser-Doppler microvascular function and ADP-induced platelet aggregation capacity were measured at baseline, 2 h after oral antiplatelet loading, and 1 day, 1 week and 1 month after stenting during chronic therapy with the same antiplatelet agent
Summary
Platelet activation is associated with the release of mediators of inflammation and oxidative stress, which stimulate leukocyte chemotaxis, aggregation and endothelial dysfunction [reviewed in [1]], impairing micro- and macrovascular function. Along with their antithrombotic benefits, clopidogrel and other P2Y12 inhibitors have been shown to have an impact on endothelial and vascular function in patients with and without coronary artery disease [2,3,4,5]. These processes assume a particular importance in the setting of coronary stenting, and even more in patients with acute coronary syndromes (ACS). In the Protecting Microcirculation During Coronary Angioplasty (PROMICRO) Randomized Study [6], the microvascular impairment induced by coronary stenting was reduced following antiplatelet therapy with prasugrel. No difference was shown between prasugrel and ticagrelor in preventing coronary microvascular injury following a ST-elevation myocardial infarction [8]
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