Sara Ariotti1, Luis Ortega-Paz2, Maarten van Leeuwen3, Salvatore Brugaletta2, Sergio Leonardi4, K Martijn Akkerhuis5, Stefano F Rimoldi1, Gladys Janssens6, Umberto Gianni4, Jan C van den Berge5, Alexios Karagiannis7, Stephan Windecker1, Marco Valgimigli8. 1. Swiss Cardiovascular Center Bern, Bern University Hospital, Bern, Switzerland. 2. Cardiovascular Clinic Institute, Hospital Clínic, University of Barcelona, IDIBAPS, Barcelona, Spain. 3. Department of Cardiology, VU University Medical Center, Amsterdam, the Netherlands; Department of Cardiology, Isala Heart Centre, Zwolle, the Netherlands. 4. Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 5. Department of Cardiology, Erasmus University Medical Center, Rotterdam, the Netherlands. 6. Department of Cardiology, VU University Medical Center, Amsterdam, the Netherlands. 7. CTU Bern, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. 8. Swiss Cardiovascular Center Bern, Bern University Hospital, Bern, Switzerland. Electronic address: marco.valgimigli@insel.ch.
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 P2Y12 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).
RCT Entities:
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 P2Y12 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).
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