Author + information
- Received March 20, 2018
- Revision received April 13, 2018
- Accepted April 13, 2018
- Published online May 24, 2018.
- Sara Ariotti, MDa,
- Luis Ortega-Paz, MDb,
- Maarten van Leeuwen, MDc,d,
- Salvatore Brugaletta, MD, PhDb,
- Sergio Leonardi, MD, MHSe,
- K. Martijn Akkerhuis, MD, PhDf,
- Stefano F. Rimoldi, MDa,
- Gladys Janssens, MDc,
- Umberto Gianni, MDe,
- Jan C. van den Berge, MDf,
- Alexios Karagiannis, PhDg,
- Stephan Windecker, MD, PhDa,
- Marco Valgimigli, MD, PhDa,∗ (, )
- on behalf of the HI-TECH Investigators
- aSwiss Cardiovascular Center Bern, Bern University Hospital, Bern, Switzerland
- bCardiovascular Clinic Institute, Hospital Clínic, University of Barcelona, IDIBAPS, Barcelona, Spain
- cDepartment of Cardiology, VU University Medical Center, Amsterdam, the Netherlands
- dDepartment of Cardiology, Isala Heart Centre, Zwolle, the Netherlands
- eDepartment of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- fDepartment of Cardiology, Erasmus University Medical Center, Rotterdam, the Netherlands
- gCTU Bern, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
- ↵∗Address for correspondence:
Dr. Marco Valgimigli, Swiss Cardiovascular Center Bern, Bern University Hospital, CH-3010, Bern, Switzerland.
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 dilatation 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).
This work was supported by a research grant from AstraZeneca. The study was designed by the principal investigator (Dr. Valgimigli), and sponsored by the Erasmus Medical Center and a nonprofit organization. The study sponsor and supporting company had no role in study design, data collection, data monitoring, analysis, interpretation, or writing of the report. CTU Bern, University of Bern, has a staff policy of not accepting honoraria or consultancy fees. However, CTU Bern is involved in the design, conduct, or analysis of clinical studies funded by not-for-profit and for-profit organizations. In particular, pharmaceutical and medical device companies provide direct funding to some of these studies. Drs. van Leeuwen and Janssens have received institutional research grant support from AstraZeneca. Dr. Brugaletta has received institutional research grant support from AstraZeneca; and speaker fees from Abbott Vascular and Boston Scientific. Dr. Leonardi has received consulting fees from AstraZeneca, Ely Lilly, The Medicines Company, and Chiesi. Dr. Rimoldi has served on the Speakers Bureau for Servier and Menarini. Dr. Windecker has received institutional research grant support from Abbott, Bracco, Biotronik, Boston Scientific, St. Jude Medical, Medtronic, and Terumo. Dr. Valgimigli has received grant support from AstraZeneca and Terumo; and personal fees from AstraZeneca, Terumo, Abbott Vascular, Bayer, Amgen, Cardinal Health, Biosensors, Abbott Vascular, and Daiichi Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received March 20, 2018.
- Revision received April 13, 2018.
- Accepted April 13, 2018.
- 2018 American College of Cardiology Foundation
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