TY - JOUR
T1 - Effects of Ticagrelor, Prasugrel, or Clopidogrel on Endothelial Function and Other Vascular Biomarkers: A Randomized Crossover Study
AU - Ariotti, Sara
AU - Ortega-Paz, Luis
AU - van Leeuwen, Maarten
AU - Brugaletta, Salvatore
AU - Leonardi, Sergio
AU - Akkerhuis, K. Martijn
AU - Rimoldi, Stefano F.
AU - Janssens, Gladys
AU - Gianni, Umberto
AU - van den Berge, Jan C.
AU - Karagiannis, Alexios
AU - Windecker, Stephan
AU - Valgimigli, Marco
AU - Frigoli, Enrico
AU - Monti, Monia
AU - Ciociano, Nestor
AU - Karagiannis, Alexios
AU - Heg, Dik
AU - Valgimigli, Marco
AU - Leonardi, Sergio
AU - van Royen, Niels
AU - Brugaletta, Salvatore
AU - Heg, Dik
AU - Leonardi, Sergio
AU - Rizzotti, Diego
AU - Mandurino Mirizzi, Alessandro
AU - van Leeuwen, Maarten
AU - Janssens, Gladys
AU - Räber, Lorenz
AU - Ariotti, Sara
AU - Valgimigli, Marco
AU - Windecker, Stephan
AU - Rimoldi, Stefano F.
AU - Rexhaj, Emrush
AU - Brugaletta, Salvatore
AU - Sabaté, Manel
AU - Ortega-Paz, Luis
AU - Akkerhuis, K. Martijn
AU - van den Berge, Jan C.
AU - HI-TECH Investigators
PY - 2018
Y1 - 2018
N2 - 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).
AB - 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).
KW - P2Y12 inhibitors
KW - adenosine
KW - endothelial function
KW - prasugrel
KW - ticagrelor
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85047180330&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29805112
U2 - 10.1016/j.jcin.2018.04.022
DO - 10.1016/j.jcin.2018.04.022
M3 - Article
C2 - 29805112
VL - 11
SP - 1576
EP - 1586
JO - JACC Cardiovascular Interventions
JF - JACC Cardiovascular Interventions
SN - 1936-8798
IS - 16
ER -