Endothelial biomarkers and platelet reactivity on ticagrelor versus clopidogrel in patients after acute coronary syndrome with and without concomitant type 2 diabetes: a preliminary observational study

Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimský P, ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39(2):119–77.

Article  PubMed  Google Scholar 

Collet JP, Thiele H, Barbato E, Barthélémy O, Bauersachs J, Bhatt DL, Dendale P, Dorobantu M, Edvardsen T, Folliguet T, Gale CP, Gilard M, Jobs A, Jüni P, Lambrinou E, Lewis BS, Mehilli J, Meliga E, Merkely B, Mueller C, Roffi M, Rutten FH, Sibbing D, Siontis GCM, ESC Scientific Document Group. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2021;42(14):1289–367.

Article  PubMed  Google Scholar 

Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA, for the PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045–57.

Article  CAS  PubMed  Google Scholar 

Bonaca MP, Braunwald E, Sabatine MS. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;373(13):1274–5.

PubMed  Google Scholar 

James S, Angiolillo DJ, Cornel JH, Erlinge D, Husted S, Kontny F, Maya J, Nicolau JC, Spinar J, Storey RF, Stevens SR, Wallentin L, for the PLATO Study Group. Ticagrelor vs. clopidogrel in patients with acute coronary syndromes and diabetes: a substudy from the PLATelet inhibition and patient Outcomes (PLATO) trial. Eur Heart J. 2010;31(24):3006–16.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bhatt DL, Bonaca MP, Bansilal S, Angiolillo DJ, Cohen M, Storey RF, Im K, Murphy SA, Held P, Braunwald E, Sabatine MS, Steg PG. Reduction in ischemic events with ticagrelor in diabetic patients with prior myocardial infarction in PEGASUS-TIMI 54. J Am Coll Cardiol. 2016;67(23):2732–40.

Article  CAS  PubMed  Google Scholar 

Ferreiro JL, Angiolillo DJ. Diabetes and antiplatelet therapy in acute coronary syndrome. Circulation. 2011;123(7):798–813.

Article  PubMed  Google Scholar 

Camm AJ, Sabbour H, Schnell O, Summaria F, Verma A. Managing thrombotic risk in patients with diabetes. Cardiovasc Diabetol. 2022;21(1):160.

Article  PubMed  PubMed Central  Google Scholar 

Hamilos M, Petousis S, Xanthopoulou I, Goudevenos J, Kanakakis J, Sitafidis G, Vavouranakis M, Skalidis E, Kochiadakis G, Lekakis J, Vardas PE, Alexopoulos D. Antiplatelet treatment in diabetic patients with acute coronary syndrome undergoing percutaneous coronary intervention: a GReek AntiPlatElet registry substudy. Coron Artery Dis. 2018;29(1):53–9.

Article  PubMed  Google Scholar 

Leiter LA, Bhatt DL, McGuire DK, Teoh H, Fox K, Simon T, Mehta SR, Lev EI, Kiss RG, Dalby AJ, Bueno H, Ridderstråle W, Himmelmann A, Prats J, Liu Y, Lee JJ, Amerena J, Kosiborod MN, Steg PG, THEMIS Steering Committee and Investigators. Diabetes-related factors and the effects of ticagrelor plus aspirin in the THEMIS and THEMIS-PCI trials. J Am Coll Cardiol. 2021;77(19):2366–77.

Article  CAS  PubMed  Google Scholar 

Blin P, Darmon P, Henry P, Guiard E, Bernard MA, Dureau-Pournin C, Maizi H, Thomas-Delecourt F, Lassalle R, Droz-Perroteau C, Moore N. Patients with stable coronary artery disease and type 2 diabetes but without prior myocardial infarction or stroke and THEMIS-like patients: real-world prevalence and risk of major outcomes from the SNDS French nationwide claims database. Cardiovasc Diabetol. 2021;20(1):229.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gurbel PA, Jeong YH, Tantry US. The dogged search for cryptic effects of ticagrelor: wishful thinking or real benefits beyond P2Y12 inhibition? Circulation. 2016;134(22):1720–3.

Article  PubMed  Google Scholar 

Reiner MF, Akhmedov A, Stivala S, Keller S, Gaul DS, Bonetti NR, Savarese G, Glanzmann M, Zhu C, Ruf W, Yang Z, Matter CM, Lüscher TF, Camici GG, Beer JH. Ticagrelor, but not clopidogrel, reduces arterial thrombosis via endothelial tissue factor suppression. Cardiovasc Res. 2017;113(1):61–9.

Article  CAS  PubMed  Google Scholar 

Torngren K, Ohman J, Salmi H, Larsson J, Erlinge D. Ticagrelor improves peripheral arterial function in patients with a previous acute coronary syndrome. Cardiology. 2013;124(4):252–8.

Article  CAS  PubMed  Google Scholar 

Hamilos M, Petousis S, Parthenakis F. Interaction between platelets and endothelium: from pathophysiology to new therapeutic options. Cardiovasc Diagn Ther. 2018;8(5):568–80.

Article  PubMed  PubMed Central  Google Scholar 

van Giezen JJ, Sidaway J, Glaves P, Kirk I, Björkman JA. Ticagrelor inhibits adenosine uptake in vitro and enhances adenosine-mediated hyperemia responses in a canine model. J Cardiovasc Pharmacol Ther. 2012;17(2):164–72.

Article  PubMed  Google Scholar 

Ohman J, Kudira R, Albinsson S, Olde B, Erlinge D. Ticagrelor induces adenosine triphosphate release from human red blood cells. Biochem Biophys Res Commun. 2012;418(4):754–8.

Article  PubMed  Google Scholar 

Armstrong D, Summers C, Ewart L, Nylander S, Sidaway JE, van Giezen JJ. Characterization of the adenosine pharmacology of ticagrelor reveals therapeutically relevant inhibition of equilibrative nucleoside transporter 1. J Cardiovasc Pharmacol Ther. 2014;19(2):209–19.

Article  CAS  PubMed  Google Scholar 

Cattaneo M, Schulz R, Nylander S. Adenosine-mediated effects of ticagrelor: evidence and potential clinical relevance. J Am Coll Cardiol. 2014;63(23):2503–9.

Article  CAS  PubMed  Google Scholar 

Bonello L, Laine M, Kipson N, Mancini J, Helal O, Fromonot J, Gariboldi V, Condo J, Thuny F, Frere C, Camoin-Jau L, Paganelli F, Dignat-George F, Guieu R. Ticagrelor increases adenosine plasma concentration in patients with an acute coronary syndrome. J Am Coll Cardiol. 2014;63(9):872–7.

Article  CAS  PubMed  Google Scholar 

Nylander S, Schulz R. Effects of P2Y12 receptor antagonists beyond platelet inhibition–comparison of ticagrelor with thienopyridines. Br J Pharmacol. 2016;173(7):1163–78.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mangiacapra F, Panaioli E, Colaiori I, Ricottini E, Lauria Pantano A, Pozzilli P, Barbato E, Di Sciascio G. Clopidogrel versus ticagrelor for antiplatelet maintenance in diabetic patients treated with percutaneous coronary intervention: results of the CLOTILDIA study (clopidogrel high dose versus ticagrelor for antiplatelet maintenance in diabetic patients). Circulation. 2016;134(11):835–7.

Article  PubMed  Google Scholar 

Jeong HS, Hong SJ, Cho SA, Kim JH, Cho JY, Lee SH, Joo HJ, Park JH, Yu CW, Lim DS. Comparison of ticagrelor versus prasugrel for inflammation, vascular function, and circulating endothelial progenitor cells in diabetic patients with non-ST-segment elevation acute coronary syndrome requiring coronary stenting: a prospective, randomized, crossover trial. JACC Cardiovasc Interv. 2017;10(16):1646–58.

Article  PubMed  Google Scholar 

Campo G, Vieceli Dalla Sega F, Pavasini R, Aquila G, Gallo F, Fortini F, Tonet E, Cimaglia P, Del Franco A, Pestelli G, Pecoraro A, Contoli M, Balla C, Biscaglia S, Rizzo P, Ferrari R. Biological effects of ticagrelor over clopidogrel in patients with stable coronary artery disease and chronic obstructive pulmonary disease. Thromb Haemost. 2017;117(6):1208–16.

Article  PubMed  PubMed Central  Google Scholar 

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, Valgimigli M, HI-TECH Investigators. Effects of ticagrelor, prasugrel, or clopidogrel on endothelial function and other vascular biomarkers: a randomized crossover study. JACC Cardiovasc Interv. 2018;11(16):1576–86.

Article  PubMed  Google Scholar 

Schnorbus B, Daiber A, Jurk K, Warnke S, Koenig J, Lackner KJ, Münzel T, Gori T. Effects of clopidogrel vs. prasugrel vs. ticagrelor on endothelial function, inflammatory parameters, and platelet function in patients with acute coronary syndrome undergoing coronary artery stenting: a randomized, blinded, parallel study. Eur Heart J. 2020;41(33):3144–52.

Article  CAS  PubMed  Google Scholar 

Guan B, Zhao L, Ma D, Fan Y, Zhang H, Wang A, Xu H. The effect of ticagrelor on endothelial function compared to prasugrel, clopidogrel, and placebo: a systematic review and meta-analysis. Front Cardiovasc Med. 2021;8:820604.

Article  PubMed  Google Scholar 

Ndrepepa G, Kastrati A, Menichelli M, Neumann FJ, Wöhrle J, Bernlochner I, Richardt G, Witzenbichler B, Sibbing D, Gewalt S, Angiolillo DJ, Hamm CW, Hapfelmeier A, Trenk D, Laugwitz KL, Schunkert H, Schüpke S, Mayer K. Ticagrelor or prasugrel in patients with acute coronary syndromes and diabetes mellitus. JACC Cardiovasc Interv. 2020;13(19):2238–47.

Article  PubMed  Google Scholar 

Angiolillo DJ, Baber U, Sartori S, Briguori C, Dangas G, Cohen DJ, Mehta SR, Gibson CM, Chandiramani R, Huber K, Kornowski R, Weisz G, Kunadian V, Oldroyd KG, Ya-Ling H, Kaul U, Witzenbichler B, Dudek D, Sardella G, Escaned J, Sharma S, Shlofmitz RA, Collier T, Pocock S, Mehran R. Ticagrelor with or without aspirin in high-risk patients with diabetes mellitus undergoing percutaneous coronary intervention. J Am Coll Cardiol. 2020;75(19):2403–13.

Article  CAS  PubMed  Google Scholar 

Cattaneo M, Lecchi A. Inhibition of the platelet P2Y12 receptor for adenosine diphosphate potentiates the antiplatelet effect of prostacyclin. J Thromb Haemost. 2007;5(3):577–82.

Article  CAS  PubMed  Google Scholar 

Kirkby NS, Lundberg MH, Chan MV, Vojnovic I, Solomon AB, Emerson M, Mitchell JA, Warner TD. Blockade of the purinergic P2Y12 receptor greatly increases the platelet inhibitory actions of nitric oxide. Proc Natl Acad Sci U S A. 2013;10(39):15782–7.

Article  Google Scholar 

Chan MV, Knowles RB, Lundberg MH, Tucker AT, Mohamed NA, Kirkby NS, Armstrong PC, Mitchell JA, Warner TD. P2Y12 receptor blockade synergizes strongly with nitric oxide and prostacyclin to inhibit platelet activation. Br J Clin Pharmacol. 2016;81(4):621–33.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sibbing D, Braun S, Jawansky S, Vogt W, Mehilli J, Schömig A, Kas

留言 (0)

沒有登入
gif