1. Effects of Ticagrelor, Prasugrel, or Clopidogrel on Endothelial Function and Other Vascular Biomarkers: A Randomized Crossover Study.
- Author
-
Ariotti S, Ortega-Paz L, van Leeuwen M, Brugaletta S, Leonardi S, Akkerhuis KM, Rimoldi SF, Janssens G, Gianni U, van den Berge JC, Karagiannis A, Windecker S, and Valgimigli M
- Subjects
- Acute Coronary Syndrome blood, Acute Coronary Syndrome physiopathology, Adenosine blood, Aged, Biomarkers blood, Clopidogrel adverse effects, Coronary Vessels physiopathology, Cross-Over Studies, Endothelium, Vascular physiopathology, Europe, Female, Humans, Male, Middle Aged, Platelet Aggregation Inhibitors adverse effects, Prasugrel Hydrochloride adverse effects, Purinergic P2Y Receptor Antagonists adverse effects, Ticagrelor adverse effects, Time Factors, Treatment Outcome, Acute Coronary Syndrome drug therapy, Clopidogrel therapeutic use, Coronary Vessels drug effects, Endothelium, Vascular drug effects, Platelet Aggregation Inhibitors therapeutic use, Prasugrel Hydrochloride therapeutic use, Purinergic P2Y Receptor Antagonists therapeutic use, Ticagrelor therapeutic use, Vasodilation drug effects
- Abstract
Objectives: The study sought to assess whether treatment with ticagrelor, as compared with prasugrel and clopidogrel, improves endothelium-dependent dilation throughout the course of the treatment and other vascular biomarkers, including systemic adenosine plasma levels., Background: The in vivo off-target effects of ticagrelor in post-acute coronary syndrome (ACS) patients remain poorly characterized., Methods: Fifty-four stable post-ACS patients were sequentially exposed to each of the 3 oral P2Y
12 inhibitors following a 3-period balanced Latin square crossover design with 4 weeks per treatment in 5 European centers. The primary endpoint was the assessment of endothelial function with pulse amplitude tonometry and expressed as reactive hyperemia index at treatment steady state. Secondary endpoints included reactive hyperemia index after loading or before maintenance regimen, systemic adenosine plasma levels, a wide set of vascular biomarkers, and ticagrelor or AR-C124910XX plasma levels throughout each ticagrelor period. In 9 patients, the evaluation of endothelial function was performed simultaneously by pulse amplitude tonometry and flow-mediated dilation., Results: Reactive hyperemia index did not differ after ticagrelor (1.970 ± 0.535) as compared with prasugrel (2.007 ± 0.640; p = 0.557) or clopidogrel (2.072 ± 0.646; p = 0.685), nor did systemic adenosine plasma levels or vascular biomarkers at any time points. P2Y12 platelet reactivity units were lower after ticagrelor as compared with clopidogrel at all time points and after maintenance dose as compared with prasugrel. Flow-mediated dilation did not differ after the maintenance dose of ticagrelor as compared with clopidogrel and prasugrel., Conclusions: Ticagrelor did not improve endothelial function or increased systemic adenosine plasma levels as compared with prasugrel and clopidogrel in stabilized patients who suffered from an ACS. (Hunting for the Off-Target Properties of Ticagrelor on Endothelial Function in Humans [HI-TECH]; NCT02587260)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF