Rationale and Design of ST-ON-SET: Assessment of Antiplatelet Effect after Ticagrelor Loading Dose in STEMI Patients and NSTEMI Patients

Hongyi Wu, Yinman Wang, Huajie Xu, Juying Qian, Junbo Ge


Background: Delayed platelet inhibition by ticagrelor has been initially documented in STEMI subjects. To the best of our knowledge, no data exists about the direct description of early onset of platelet inhibition after ticagrelor loading dose (LD) in different clinical forms of ACS, especially in Chinese patients. The ST-ON-SET study is designed to address this unmet need.

Method/Design: The ST-ON-SET study is a single center, prospective, observational, open-label, investigator-initiated study. Platelet inhibition assessed by Light transmittance aggregometry (LTA) and plasma concentrations of ticagrelor and its metabolites would be investigated serially. The primary outcome is the inhibition of platelet aggregation measured by LTA at 2 hours after ticagrelor LD. Moreover, baseline inflammatory and thrombotic biomarkers would be measured to investigate the potential underlying influences of platelet inhibition.

Conclusion: The study is designed to characterize pharmacokinetic and pharmacodynatic profiles of ticagrelor LD in Chinese STEMI and NSTEMI patients. Furthermore, preliminary investigation of the underlying mechanism of initial delayed platelet inhibition by ticagrelor would be conducted.


acute coronary syndrome; ticagrelor; pharmacokinetics; pharmacodynamics

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Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361:1045–1057. DOI: 10.1056/NEJMoa0904327

Teng R, Oliver S, Hayes MA, et al. Absorption, distribution, metabolism, and excretion of ticagrelor in healthy subjects. Drug Metab Dispos. 2010;38:1514–1521. DOI: 10.1124/dmd.110.032250

Gurbel PA, Bliden KP, Butler K, et al. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009;120:2577–2585. DOI: 10.1161/CIRCULATIONAHA.109.912550

Parodi G, Valenti R, Bellandi B, et al. Comparison of prasugrel and ticagrelor loading doses in ST-segment elevation myocardial infarction patients: RAPID (Rapid Activity of Platelet Inhibitor Drugs) primary PCI study. J Am Coll Cardiol. 2013;61(15):1601-6. DOI: 10.1016/j.jacc.2013.01.024

Armstrong PW, Siha H, Fu Y, et al. ST-elevation acute coronary syndromes in the Platelet Inhibition and Patient Outcomes (PLATO) trial: insights from the ECG substudy. Circulation. 2012;125:514–521. DOI: 10.1161/CIRCULATIONAHA.111.047530

Thygesen K, Alpert JS, White HD, et al. Universal definition of myocardial infarction. Circulation 2007;116:2634-2653. DOI: 10.1161/CIRCULATIONAHA.107.187397

Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical trials : a consensus report from the Bleeding Academic Research Consortium. Circulation 2011, 123(23):2736–2747. DOI: 10.1161/CIRCULATIONAHA.110.009449

Heestermans AA, van Werkum JW, Taubert D, et al. Impaired bioavailability of clopidogrel in patients with a ST-segment elevation myocardial infarction. Thromb Res. 2008;122(6):776-81. DOI: 10.1016/j.thromres.2008.01.021

De Pietri L, Montalti R, Begliomini B, et al. Thromboelastographic changes in liver and pancreatic cancer surgery: hypercoagulability, hypocoagulability or normocoagulability? Eur J Anaesthesiol. 2010;27(7):608-16. DOI: 10.1097/EJA.0b013e328334df31

Perrin J, Charron C, François JH, et al. Coagulation phenotypes in septic shock as evaluated by calibrated automated thrombography. Shock. 2015;43(1):74-9. DOI: 10.1097/SHK.0000000000000271

Gurbel PA, Bliden KP, Guyer K, et al. Delayed thrombin-induced platelet-fibrin clot generation by clopidogrel: a new dose-related effect demonstrated by thrombelastography in patients undergoing coronary artery stenting. Thromb Res. 2007;119(5):563-70. DOI: 10.1016/j.thromres.2006.05.006

Wu H,Qian J,Wang Q,et al. Thrombin induced platelet-fibrin clot strength measured by thrombelastography is a novel marker of platelet activation in acute myocardial infarction. Int J Cardiol. 2014,172(1):e24-e25. DOI: 10.1016/j.ijcard.2013.12.092

Jeong YH, Bliden KP, Shuldiner AR, Tantry US, Gurbel PA. Thrombin-induced platelet-fibrin clot strength: relation to high on-lopidogrel platelet reactivity, genotype, and post-percutaneous coronary intervention outcomes. Thromb Haemost. 2014, 111(4):713-24. DOI: 10.1160/TH13-08-0643

Morel O, El Ghannudi S, Hess S,et al. The extent of P2Y12 inhibition by clopidogrel in diabetes mellitus patients with acute coronary syndrome is not related to glycaemic control: roles of white blood cell count and body weight. Thromb Haemost. 2012,108(2):338-48. DOI: 10.1160/TH11-12-0876

Weber M, Bhatt DL, Brennan DM, et al. High-sensitivity C-reactive protein and clopidogrel treatment in patients at high risk of cardiovascular events: a substudy from the CHARISMA trial. Heart. 2011,97(8):626-31. DOI: 10.1136/hrt.2010.210419

Bonello L, Berbis J, Laine M, et al. Biological efficacy of a 600 mg loading dose of clopidogrel in ST-elevation myocardial infarction. Thromb Haemost. 2012,108(1):101-15. DOI: 10.1160/TH12-02-0125

Libby P,Ridker PM,Hansson GK. Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol. 2009,54(23):2129-2138. DOI: 10.1016/j.jacc.2009.09.009

Shewan LG, Coats AJS, Henein M. Requirements for ethical publishing in biomedical journals. International Cardiovascular Forum Journal 2015;2:2 DOI: 10.17987/icfj.v2i1.4

DOI: https://doi.org/10.17987/icfj.v8i0.320

Copyright (c) 2016 Hongyi Wu, Yinman Wang, Huajie Xu, Juying Qian, Junbo Ge

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