2,238
Views
9
CrossRef citations to date
0
Altmetric
Invited Article: Celebrating the achievements of Professor Stan Heptinstall, Founder and Editor-in-Chief of Platelets (1990–2015)

The future of P2Y12 receptor antagonists

&
Pages 392-398 | Received 04 May 2015, Accepted 04 May 2015, Published online: 04 Jun 2015

References

  • Wijeyeratne YD, Heptinstall S. Anti-platelet therapy: ADP receptor antagonists. Br J Clin Pharmacol 2011;72:647–657
  • Storey RF, Sanderson HM, White AE, May JA, Cameron KE, Heptinstall S. The central role of the P(2T) receptor in amplification of human platelet activation, aggregation, secretion and procoagulant activity. Br J Haematol 2000;110:925–934
  • Gent M, Blakely JA, Easton DJ, Ellis DJ, Hachinkski VC, Harbison JW, Panak E, Roberts RS, Sicurella J, Turpie AG. The Canadian American ticlopidine study (CATS) in thromboembolic stroke. Lancet 1989;333:1215–1220
  • Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK, Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494–502
  • Sabatine MS, Cannon CP, Gibson CM, López-Sendón JL, Montalescot G, Theroux P, Claeys MJ, Cools F, Hill KA, Skene AM, et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med 2005;352:1179–1189
  • Steinhubl SR, Berger PB, Mann JT, Fry ETA, DeLago A, Wilmer C, Topol EJ, Observation CREDO Investigators Clopidogrel for the Reduction of Events During. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: A randomized controlled trial. JAMA 2002;288:2411–2420
  • Breet NJ, Van Werkum JW, Bouman HJ, Kelder JC, Ruven HJT, Bal ET, Deneer VH, Harmsze AM, van der Heyden JAS, Rensing BJWM, et al. Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. JAMA 2010;303:754–762
  • Michelson AD, Frelinger AL, Braunwald E, Downey WE, Angiolillo DJ, Xenopoulos NP, Jakubowski JA, Li Y, Murphy SA, Qin J, et al., for the TRITON-TIMI 38 Investigators. Pharmacodynamic assessment of platelet inhibition by prasugrel vs. clopidogrel in the TRITON-TIMI 38 trial. Eur Heart J 2009;30:1753–1763
  • Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann F-J, Ardissino D, De Servi S, Murphy SA, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001–2015
  • Wijeyeratne YD, Joshi R, Heptinstall S. Ticagrelor: A P2Y12 antagonist for use in acute coronary syndromes. Expert Rev Clin Pharmacol 2012;5:257–269
  • Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045–1057
  • Kazui M, Nishiya Y, Ishizuka T, Hagihara K, Farid NA, Okazaki O, Ikeda T, Kurihara A. Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug Metab Dispos 2009;38:92–99
  • Thomas MR, Storey RF. Optimal management of antiplatelet therapy and proton pump inhibition following percutaneous coronary intervention. Curr Treat Options Cardiovasc Med 2011;14:24–38
  • Thomas MR, Storey RF. Genetics of response to antiplatelet therapy. Prog Mol Biol Transl Sci 2014;124:123–153
  • Farid NA, Kurihara A, Wrighton SA. Metabolism and disposition of the thienopyridine antiplatelet drugs ticlopidine, clopidogrel, and prasugrel in humans. J Clin Pharmacol 2013;50:126–142
  • Rehmel JLF. Interactions of two major metabolites of prasugrel, a thienopyiridne antiplatelet agent, with the cytochromes P450. Drug Metab Dispos 2006;34:600–607
  • Payne CD, Li YG, Small DS, Ernest CS, Farid NA, Jakubowski JA, Brandt JT, Salazar DE, Winters KJ. Increased active metabolite formation explains the greater platelet inhibition with prasugrel compared to high-dose clopidogrel. J Cardiovasc Pharmacol Ther 2007;50:555–562
  • Husted SE, Storey RF, Bliden K, Tantry US, Hoimark L, Butler K, Wei C, Teng R, Gurbel PA. Pharmacokinetics and pharmacodynamics of ticagrelor in patients with stable coronary artery disease results from the ONSET–OFFSET and RESPOND studies. Clin Pharmacokinet 2012;51:397–409
  • Teng R, Butler K. Effect of the CYP3A inhibitors, diltiazem and ketoconazole, on ticagrelor pharmacokinetics in healthy volunteers. J Drug Assess 2013;2:30–39
  • Thomas MR, Wijeyeratne YD, May JA, Johnson A, Heptinstall S, Fox SC. A platelet P-selectin test predicts adverse cardiovascular events in patients with acute coronary syndromes treated with aspirin and clopidogrel. Platelets 2014;25:612–618
  • Tantry US, Bonello L, Aradi D, Price MJ, Jeong Y-H, Angiolillo DJ, Stone GW, Curzen N, Geisler T, Berg Ten J, et al. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding. J Am Coll Cardiol 2013;62:2261–2273
  • Aradi D, Kirtane A, Bonello L, Gurbel PA, Tantry US, Huber K, Freynhofer MK, Berg Ten J, Janssen P, Angiolillo DJ, et al. Bleeding and stent thrombosis on P2Y12-inhibitors: Collaborative analysis on the role of platelet reactivity for risk stratification after percutaneous coronary intervention. Eur Heart J 2015; ePub ahead of print
  • Storey RF. More transparency for a therapeutic window in platelet P2Y12 inhibition? Eur Heart J, in press
  • Price MJ. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention the GRAVITAS randomized trial. JAMA 2011;305:1097–1105
  • Trenk D, Stone GW, Gawaz M, Kastrati A, Angiolillo DJ, Müller U, Richardt G, Jakubowski JA, Neumann F-J. A randomized trial of prasugrel versus clopidogrel in patients with high platelet reactivity on clopidogrel after elective percutaneous coronary intervention with implantation of drug-eluting stents. J Am Coll Cardiol 2012;59:2159–2164
  • Collet J-P, Cuisset T, Rangé G, Cayla G, Elhadad S, Pouillot C, Henry P, Motreff P, Carrié D, Boueri Z, et al. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 2012;367:2100–2109
  • Storey RF, Angiolillo DJ, Patil SB, Desai B, Ecob R, Husted S, Emanuelsson H, Cannon CP, Becker RC, Wallentin L. Inhibitory effects of ticagrelor compared with clopidogrel on platelet function in patients with acute coronary syndromes: The PLATO (PLATelet inhibition and patient Outcomes) PLATELET substudy. J Am Coll Cardiol 2010;56:1456–1462
  • Lindholm D, Varenhorst C, Cannon CP, Harrington RA, Himmelmann A, Maya J, Husted S, Gabriel Steg P, Cornel JH, Storey RF, et al. Ticagrelor vs. clopidogrel in patients with non-ST-elevation acute coronary syndrome with or without revascularization: Results from the PLATO trial. Eur Heart J 2014;35:2083–2093
  • Alexopoulos D, Xanthopoulou I, Storey RF, Bliden K, Tantry US, Angiolillo DJ, Gurbel PA. Platelet reactivity during ticagrelor maintenance therapy: A patient-level data meta-analysis. Am Heart J 2014;168:530–536
  • Price MJ, Walder JS, Baker BA, Heiselman DE, Jakubowski JA, Logan DK, Winters KJ, Li W, Angiolillo DJ. Recovery of platelet function after discontinuation of prasugrel or clopidogrel maintenance dosing in aspirin-treated patients with stable coronary disease: The recovery trial. J Am Coll Cardiol 2012;59:2338–2343
  • Gurbel PA, Bliden KP, Butler K, Tantry US, Gesheff T, Wei C, Teng R, Antonino MJ, Patil SB, Karunakaran A, 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
  • Varenhorst C, Scirica BM, Hogue CW, Åsenblad N, Storey RF, Steg PG, Horrow J, Mahaffey KW, Becker RC, James S, et al. Factors contributing to the lower mortality with ticagrelor compared with clopidogrel in patients undergoing coronary artery bypass surgery. J Am Coll Cardiol 2012;60:1623–1630
  • Angiolillo DJ. Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery a randomized controlled trial. JAMA 2012;307:265–274
  • Nylander S, Pehrsson S, Inghardt T, Antonsson T, Svensson P, Sjögren T, Öster L, Janefeldt A, Sandinge A-S, Newton P, et al. A specific antidote for ticagrelor. J Am Coll Cardiol 2015;65:A253
  • Brandt JT, Payne CD, Wiviott SD, Weerakkody G, Farid NA, Small DS, Jakubowski JA, Naganuma H, Winters KJ. A comparison of prasugrel and clopidogrel loading doses on platelet function: Magnitude of platelet inhibition is related to active metabolite formation. Am Heart J 2007;153:e9–e16
  • Alexopoulos D, Xanthopoulou I, Gkizas V, Kassimis G, Theodoropoulos KC, Makris G, Koutsogiannis N, Damelou A, Tsigkas G, Davlouros P, Hahalis G. Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with ST-segment-elevation myocardial infarction. Circ Cardiovasc Interv 2012;5:797–804
  • Morton AC, Hossain R, Ecob R, Walker J, Gunn J. Morphine delays the onset of action of prasugrel in patients with prior history of St Elevation Myocardial Infarction. Circulation 2013;128:A11449
  • Parodi G, Bellandi B, Xanthopoulou I, Capranzano P, Capodanno D, Valenti R, Stavrou K, Migliorini A, Antoniucci D, Tamburino C, Alexopoulos D. Morphine is associated with a delayed activity of oral antiplatelet agents in patients with ST-Elevation acute myocardial infarction undergoing primary percutaneous coronary intervention. Circ Cardiovasc Interv 2015;8:e001593
  • Parodi G, Xanthopoulou I, Bellandi B, Gkizas V, Valenti R, Karanikas S, Migliorini A, Angelidis C, Abbate R, Patsilinakos S, et al. Ticagrelor crushed tablets administration in STEMI patients: The MOJITO study. J Am Coll Cardiol 2015;65:511–512
  • Angiolillo DJ, Schneider DJ, Bhatt DL, French WJ, Price MJ, Saucedo JF, Shaburishvili T, Huber K, Prats J, Liu T, et al. Pharmacodynamic effects of cangrelor and clopidogrel: The platelet function substudy from the cangrelor versus standard therapy to achieve optimal management of platelet inhibition (CHAMPION) trials. J Thromb Thrombolysis 2012;34:44–55
  • Steg PG, Bhatt DL, Hamm CW, Stone GW, Gibson CM, Mahaffey KW, Leonardi S, Liu T, Skerjanec S, Day JR, et al. Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: A pooled analysis of patient-level data. Lancet 2013;382:1981–1992
  • Welsh RC, Rao SV, Zeymer U, Thompson VP, Huber K, Kochman J, McClure MW, Gretler DD, Bhatt DL, Gibson CM, et al., on behalf of the INNOVATE-PCI Investigators. A randomized, double-blind, active-controlled phase 2 trial to evaluate a novel selective and reversible intravenous and oral P2Y12 inhibitor elinogrel versus clopidogrel in patients undergoing nonurgent percutaneous coronary intervention: The INNOVATE-PCI trial. Circ Cardiovasc Interv 2012;5:336–346
  • Steinbuhl SR, Oh JJ, Oestreich JH, Ferraris S, Charnigo R, Akers W. Transitioning patients from cangrelor to clopidogrel: Pharmacodynamic evidence of a competitive effect. Thromb Res 2008;121:527–534
  • Schneider DJ, Seecheran N, Raza SS, Keating FK, Gogo P. Pharmacodynamic effects during the transition between cangrelor and prasugrel. Coron Artery Dis 2015;26:42–48
  • Dovlatova NL, Jakubowski JA, Sugidachi A, Heptinstall S. The reversible P2Y antagonist cangrelor influences the ability of the active metabolites of clopidogrel and prasugrel to produce irreversible inhibition of platelet function. J Thromb Haemost 2008;6:1153–1159
  • Cattaneo M, Faioni EM. Why does ticagrelor induce dyspnea? Thromb Haemost 2012;108:1031–1036
  • Armstrong D, Summers C, Ewart L, Nylander S, Sidaway JE, van Giezen JJJ. Characterization of the adenosine pharmacology of ticagrelor reveals therapeutically relevant inhibition of equilibrative nucleoside transporter 1. J Cardiovasc Pharmacol Ther 2014;19:209–219
  • Bonello L, Laine M, Kipson N, Mancini J, Helal O, Fromonot J, Gariboldi V, Condo J, Thuny F, Frere C, et al. Ticagrelor increases adenosine plasma concentration in patients with an acute coronary syndrome. J Am Coll Cardiol 2014;63:872–877
  • Wittfeldt A, Emanuelsson H, Brandrup-Wognsen G, van Giezen JJJ, Jonasson J, Nylander S, Gan L-M. Ticagrelor enhances adenosine-induced coronary vasodilatory responses in humans. J Am Coll Cardiol 2013;61:723–727
  • Varenhorst C, Alström U, Braun OO, Storey RF, Mahaffey KW, Bertilsson M, Cannon CP, Scirica BM, Himmelmann A, James SK, et al. Causes of mortality with ticagrelor compared with clopidogrel in acute coronary syndromes. Heart 2014;100:1762–1769
  • Roe MT, Armstrong PW, Fox KAA, White HD, Prabhakaran D, Goodman SG, Cornel JH, Bhatt DL, Clemmensen P, Martinez F, et al. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med 2012;367:1297–1309
  • James SK, Roe MT, Cannon CP, Cornel JH, Horrow J, Husted S, Katus H, Morais J, Steg PG, Storey RF, et al., PLATO Study Group. Ticagrelor versus clopidogrel in patients with acute coronary syndromes intended for non-invasive management: Substudy from prospective randomised PLATelet inhibition and patient Outcomes (PLATO) trial. BMJ 2011;342:d3527
  • Hamm CW, Bassand J-P, Agewall S, Bax J, Boersma E, Bueno H, Caso P, Dudek D, Gielen S, Huber K, et al. ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2011;32:2999–3054
  • Steg PG, James SK, Atar D, Badano LP, Blömstrom-Lundqvist C, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernández-Avilés F, et al. ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012;32:2569–2619
  • Mauri L, Kereiakes DJ, Yeh RW, Driscoll-Shempp P, Cutlip DE, Steg PG, Normand S-LT, Braunwald E, Wiviott SD, Cohen DJ, et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med 2014;371:2155–2166
  • Navarese EP, Andreotti F, Schulze V, Ko odziejczak M, Buffon A, Brouwer M, Costa F, Kowalewski M, Parati G, Lip GYH, et al. Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stents: Meta-analysis of randomised controlled trials. BMJ 2015;350:h1618
  • Bonaca MP, Bhatt DL, Cohen M, Steg PG, Storey RF, Jensen EC, Magnani G, Bansilal S, Fish MP, Im K, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015 372:1791–1800
  • Montalescot G, Bolognese L, Dudek D, Goldstein P, Hamm C, Tanguay J-F, Berg ten JM, Miller DL, Costigan TM, Goedicke J, Silvain J, et al. Pretreatment with prasugrel in non-ST-segment elevation acute coronary syndromes. N Engl J Med 2013;369:999–1010
  • Montalescot G, van't Hof AW, Lapostolle F, Silvain J, Lassen JF, Bolognese L, Cantor WJ, Cequier A, Chettibi M, Goodman SG, et al. Prehospital ticagrelor in ST-segment elevation myocardial infarction. N Engl J Med 2014;371:1016–1027
  • Storey RF, James SK, Siegbahn A, Varenhorst C, Held C, Ycas J, Husted SE, Cannon CP, Becker RC, Steg PG, et al. Lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the PLATO study. Platelets 2014;25:517–525
  • Thomas MR, Storey RF. Impact of aspirin dosing on the effects of P2Y12 inhibition in patients with acute coronary syndromes. J Cardiovasc Transl Res 2014;7:19–28
  • Tricoci P, Huang Z, Held C, Moliterno DJ, Armstrong PW, Van de Werf F, White HD, Aylward PE, Wallentin L, Chen E, et al. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med 2012;366:20–33
  • Heptinstall S, Espinosa DI, Manolopoulos P, Glenn JR, White AE, Johnson A, Dovlatova N, Fox SC, May JA, Hermann D, et al. DG-041 inhibits the EP3 prostanoid receptor – a new target for inhibition of platelet function in atherothrombotic disease. Platelets 2008;19:605–613
  • Iyú D, Glenn JR, White AE, Fox SC, Dovlatova N, Heptinstall S. P2Y12 and EP3 antagonists promote the inhibitory effects of natural modulators of platelet aggregation that act via cAMP. Platelets 2011;22:504–515
  • Iyú D, Glenn JR, White AE, Johnson A, Heptinstall S, Fox SC. The role of prostanoid receptors in mediating the effects of PGE3 on human platelet function. Thromb Haemost 2012;107:797–799
  • Glenn JR, White AE, Iyú D, Heptinstall S. PGE(2) reverses G(s)-mediated inhibition of platelet aggregation by interaction with EP3 receptors, but adds to non-G(s)-mediated inhibition of platelet aggregation by interaction with EP4 receptors. Platelets 2012;23:344–351
  • Fox SC, May JA, Johnson A, Hermann D, Strieter D, Hartman D, Heptinstall S. Effects on platelet function of an EP3 receptor antagonist used alone and in combination with a P2Y12 antagonist both in-vitro and ex-vivo in human volunteers. Platelets 2013;24:392–400
  • Tilly P, Charles A-L, Ludwig S, Slimani F, Gross S, Meilhac O, Geny B, Stefansson K, Gurney ME, Fabre J-E. Blocking the EP3 receptor for PGE2 with DG-041 decreases thrombosis without impairing haemostatic competence. Cardiovasc Res 2014;101:482–491

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.