Tackling the gap in platelet inhibition with oral antiplatelet agents in high-risk patients undergoing percutaneous coronary intervention

References

• Capodanno D, Alfonso F, Levine GN, et al. ACC/AHA Versus ESC Guidelines on Dual Antiplatelet Therapy: JACC Guideline Comparison. J Am Coll Cardiol. 2018;72(23):2915–2931.
   PubMed Web of Science ®Google Scholar
• Storey RF, Angiolillo DJ, Patil SB, et al. 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(18):1456–1462.
   PubMed Web of Science ®Google Scholar
• Michelson AD, Frelinger AL, Braunwald E,,, et al. Pharmacodynamic assessment of platelet inhibition by prasugrel vs. clopidogrel in the TRITON-TIMI 38 trial. Eur Heart J. 2009;30(14):1753–1763.
   PubMed Web of Science ®Google Scholar
• Wiviott SD, Braunwald E, McCabe CH, et al., TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 357(20): 2001–2015. 2007. .
   PubMed Web of Science ®Google Scholar
• Wallentin L, Becker RC, Budaj A, et al., PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 361(11): 1045–1057. 2009.
   PubMed Web of Science ®Google Scholar
• Franchi F, Angiolillo DJ. Novel antiplatelet agents in acute coronary syndrome. Nat Rev Cardiol. 2015;12(1):30–47.
   PubMed Web of Science ®Google Scholar
• Sibbing D, Aradi D, Alexopoulos D, et al., Updated expert consensus statement on platelet function and genetic testing for guiding P2Y12 receptor inhibitor treatment in Percutaneous coronary intervention. JACC Cardiovasc Interv. 12(16): 1521–1537. 2019.
   PubMed Web of Science ®Google Scholar
• Alexopoulos D, Xanthopoulou I, Gkizas V, et al. Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with ST-segment-elevation myocardial infarction. Circ Cardiovasc Interv. 2012;5(6):797–804. .
   PubMed Web of Science ®Google Scholar
• 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):1601–1606. .
   PubMed Web of Science ®Google Scholar
• Breet NJ, Van Werkum JW, Bouman HJ, et al. The relationship between platelet reactivity and infarct-related artery patency in patients presenting with a ST-elevation myocardial infarction. Thromb Haemost. 2011;106(8):331–336.
   PubMedGoogle Scholar
• Franchi F, Rollini F, Angiolillo DJ, Rollini F and Angiolillo DJ. Antithrombotic therapy for patients with STEMI undergoing primary PCI. Nat Rev Cardiol. 2017;14(6):361–379.
   PubMed Web of Science ®Google Scholar
• Tavenier AH, Hermanides RS, Fabris E, et al. Bridging the gap: current and future insights for improving suboptimal platelet inhibition in STEMI. Int J Cardiol. 2021;328:40–45.
   PubMed Web of Science ®Google Scholar
• Jambhekar SS, Breen PJ. Drug dissolution: significance of physicochemical properties and physiological conditions. Drug Discov Today. 2013;18(23–24):1173–1184.
   PubMed Web of Science ®Google Scholar
• Vrbanac H, Trontelj J, Berglez S, et al. The biorelevant simulation of gastric emptying and its impact on model drug dissolution and absorption kinetics. Eur J Pharm Biopharm. 2020;149:113–120.
   PubMed Web of Science ®Google Scholar
• Reilly PM, Wilkins KB, Fuh KC, et al. The mesenteric hemodynamic response to circulatory shock: an overview. Shock. 2001;15(5):329–343. .
   PubMed Web of Science ®Google Scholar
• Gasbarrini G, Montalto M. Structure and function of tight junctions. Role in intestinal barrier. Ital J Gastroenterol Hepatol. 1999;31(6):481–488.
   PubMedGoogle Scholar
• Chen JDZ, Yin J, Wei W. Electrical therapies for gastrointestinal motility disorders. Expert Rev Gastroenterol Hepatol. 2017;11(5):407–418.
   PubMed Web of Science ®Google Scholar
• Bonello L, Laine M, Camoin-Jau L, et al. Onset of optimal P2Y12-ADP receptor blockade after ticagrelor and prasugrel intake in Non-ST elevation acute coronary syndrome. Thromb Haemost. 2015;114(10):702–707.
   PubMedGoogle Scholar
• Wakabayashi S, Kitahara H, Nishi T, et al. Platelet inhibition after loading dose of prasugrel in patients with ST-elevation and non-ST-elevation acute coronary syndrome. Cardiovasc Interv Ther. 2018;33(3):239–246.
   PubMed Web of Science ®Google Scholar
• Taubert D, Kastrati A, Harlfinger S, et al. Pharmacokinetics of clopidogrel after administration of a high loading dose. Thromb Haemost. 2004;92(8):311–316.
   PubMedGoogle Scholar
• 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):776–781.
   PubMed Web of Science ®Google Scholar
• Franchi F, Rollini F, Cho JR, et al. Impact of escalating loading dose regimens of ticagrelor in patients with ST-Segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: results of a prospective randomized Pharmacokinetic and pharmacodynamic investigation. JACC Cardiovasc Interv. 2015;8(11):1457–1467.
   PubMed Web of Science ®Google Scholar
• Husted SE, Storey RF, Bliden K, et al. Pharmacokinetics and pharmacodynamics of ticagrelor in patients with stable coronary artery disease: results from the ONSET-OFFSET and RESPOND studies. Clin Pharmacokinet. 2012;51(6):397–409.
   PubMed Web of Science ®Google Scholar
• Cappell MS. Intestinal (mesenteric) vasculopathy. II. Ischemic colitis and chronic mesenteric ischemia. Gastroenterol Clin North Am. 1998;27:827–860.
   PubMed Web of Science ®Google Scholar
• Scott RB, Maric M. The effect of atrial natriuretic peptide on small intestinal contractility and transit. Peptides. 1991;12(4):799–803.
   PubMed Web of Science ®Google Scholar
• Ws N, Rc H, Wilson J, et al. Inhibition of gastric emptying and drug absorption by narcotic analgesics. Br J Clin Pharmacol. 1975;2(6):509–513.
   PubMed Web of Science ®Google Scholar
• Parodi G, Bellandi B, Xanthopoulou I, et al. Morphine is associated with a delayed activity of oral antiplatelet agents in patients with STelevation acute myocardial infarction undergoing primary percutaneous coronary intervention. Circ Cardiovasc Interv. 2014;8(1):e001593.
   PubMed Web of Science ®Google Scholar
• Hobl EL, Stimpfl T, Ebner J, et al. Morphine decreases clopidogrel concentrations and effects: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol. 2014;63(7):630–635.
   PubMed Web of Science ®Google Scholar
• Hobl EL, Reiter B, Schoergenhofer C, et al. Morphine interaction with prasugrel: a double-blind, cross-over trial in healthy volunteers. Clin Res Cardiol. 2016;105(4):349–355.
   PubMed Web of Science ®Google Scholar
• Thomas MR, Morton AC, Hossain R, et al. Morphine delays the onset of action of prasugrel in patients with prior history of ST-elevation myocardial infarction. Thromb Haemost. 2016;116(7):96–102.
   PubMedGoogle Scholar
• Silvain J, Storey RF, Cayla G, et al. P2Y12 receptor inhibition and effect of morphine in patients undergoing primary PCI for ST-segment elevation myocardial infarction. The PRIVATE-ATLANTIC study. Thromb Haemost. 2016;116(8):369–378.
   PubMedGoogle Scholar
• Kubica J, Adamski P, Ostrowska M, et al. Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the randomized, double-blind, placebo-controlled IMPRESSION trial. Eur Heart J. 2016;37(3):245–252.
   PubMed Web of Science ®Google Scholar
• McEvoy JW, Ibrahim K, Kickler TS, et al. Effect of intravenous fentanyl on ticagrelor absorption and platelet inhibition among patients undergoing percutaneous coronary intervention: the PACIFY randomized clinical trial (Platelet Aggregation With Ticagrelor Inhibition and Fentanyl). Circulation. 2018;137(3):307–309.
   PubMed Web of Science ®Google Scholar
• Alexopoulos D, Bhatt DL, Hamm CW, et al. Early P2Y12 inhibition in ST-segment elevation myocardial infarction: bridging the gap. Am Heart J. 2015;170(1):3–12.
   PubMed Web of Science ®Google Scholar
• Capodanno D, Angiolillo DJ. Reviewing the controversy surrounding pre-treatment with P2Y12 inhibitors in acute coronary syndrome patients. Expert Rev Cardiovasc Ther. 2016;14(7):811–820.
   PubMed Web of Science ®Google Scholar
• Montalescot G, Bolognese L, Dudek D, et al., Pretreatment with prasugrel in non-ST-segment elevation acute coronary syndromes. N Engl J Med. 369(11): 999–1010. 2013.
   PubMed Web of Science ®Google Scholar
• Tarantini G, Mojoli M, Varbella F, et al., Timing of oral P2Y12 inhibitor administration in patients with Non-ST-Segment elevation acute coronary syndrome. J Am Coll Cardiol. 2020;76(21): 2450–2459.
   PubMed Web of Science ®Google Scholar
• Schüpke S, Neumann FJ, Menichelli M, et al., Ticagrelor or Prasugrel in Patients with acute coronary syndromes. N Engl J Med. 2019;381(16): 1524–1534.
   PubMed Web of Science ®Google Scholar
• Collet JP, Thiele H, Barbato E, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2021;42:1289–1367.
   PubMed Web of Science ®Google Scholar
• Montalescot G, Van ‘T Hof AW, Lapostolle F, et al., Prehospital ticagrelor in ST-segment elevation myocardial infarction. N Engl J Med. 371(11): 1016–1027. 2014.
   PubMed Web of Science ®Google Scholar
• Jernberg T, Payne CD, Winters KJ, et al. Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease. Eur Heart J. 2006;27(10):1166–1173.
   PubMed Web of Science ®Google Scholar
• Butler K, Teng R. Pharmacokinetics, pharmacodynamics, safety and tolerability of multiple ascending doses of ticagrelor in healthy volunteers. Br J Clin Pharmacol. 2010;70(1):65–77.
   PubMed Web of Science ®Google Scholar
• Fukushima K, Kobayashi Y, Kitahara H, et al. Effect of 150-mg vs 300-mg loading doses of clopidogrel on platelet function in Japanese patients undergoing coronary stent placement. Circ J. 2008;72(8):1282–1284.
   PubMed Web of Science ®Google Scholar
• Von Beckerath N, Taubert D, Pogatsa-Murray G, et al. Absorption, metabolization, and antiplatelet effects of 300-, 600-, and 900-mg loading doses of clopidogrel: results of the ISAR-CHOICE (Intracoronary Stenting and Antithrombotic Regimen: choose Between 3 High Oral Doses for Immediate Clopidogrel Effect) Trial. Circulation. 2005;112(19):2946–2950.
   PubMed Web of Science ®Google Scholar
• Montalescot G, Sideris G, Meuleman C, et al. A randomized comparison of high clopidogrel loading doses in patients with non-ST-segment elevation acute coronary syndromes: the ALBION (Assessment of the Best Loading Dose of Clopidogrel to Blunt Platelet Activation, Inflammation and Ongoing Necrosis) trial. J Am Coll Cardiol. 2006;48(5):931–938.
   PubMed Web of Science ®Google Scholar
• Alexopoulos D, Gkizas V, Patsilinakos S, et al. Double versus standard loading dose of ticagrelor: onset of antiplatelet action in patients with STEMI undergoing primary PCI [letter]. J Am Coll Cardiol. 2013;62(10):940–941.
   PubMed Web of Science ®Google Scholar
• Parodi G, Bellandi B, Valenti R, et al. Comparison of double (360 mg) ticagrelor loading dose with standard (60 mg) prasugrel loading dose in ST-elevation myocardial infarction patients: the Rapid Activity of Platelet Inhibitor Drugs (RAPID) primary PCI 2 study. Am Heart J. 2014;167(6):909–914.
   PubMed Web of Science ®Google Scholar
• Alexopoulos D, Makris G, Xanthopoulou I, et al. Onset of antiplatelet action with high (100 mg) versus standard (60 mg) loading dose of prasugrel in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention: pharmacodynamic study. Circ Cardiovasc Interv. 2014;7(2):233–239.
   PubMed Web of Science ®Google Scholar
• Liu HL, Wei YJ, Ding P, et al. Antiplatelet effect of different loading doses of ticagrelor in patients with Non-ST-Elevation acute coronary syndrome undergoing percutaneous coronary intervention: the APELOT trial. Can J Cardiol. 2017;33(12):1675–1682.
   PubMed Web of Science ®Google Scholar
• Crean B, Finnie C, Crosby A. Evaluation of crushed ticagrelor tablet doses: recovery following crushing and naso-gastric tube passage ex vivo. Drugs R D. 2013;13(2):153–157.
   PubMedGoogle Scholar
• Teng R, Carlson G, Hsia J. An open-label, randomized bioavailability study with alternative methods of administration of crushed ticagrelor tablets in healthy volunteers. Int J Clin Pharmacol Ther. 2015;53(2):182–189.
   PubMed Web of Science ®Google Scholar
• Parodi G, Xanthopoulou I, Bellandi B, et al. Ticagrelor crushed tablets administration in STEMI patients: the MOJITO study. J Am Coll Cardiol. 2015;65(5):511–512.
   PubMed Web of Science ®Google Scholar
• Alexopoulos D, Barampoutis N, Gkizas V, et al. Crushed versus integral tablets of ticagrelor in ST-segment elevation myocardial infarction patients: a randomized pharmacokinetic/pharmacodynamic study. Clin Pharmacokinet. 2016;55(3):359–367.
   PubMed Web of Science ®Google Scholar
• Venetsanos D, Sederholm Lawesson S, Swahn E, et al. Chewed ticagrelor tablets provide faster platelet inhibition compared to integral tablets: the inhibition of platelet aggregation after administration of three different ticagrelor formulations (IPAAD-Tica) study, a randomised controlled trial. Thromb Res. 2017;149:88–94.
   PubMed Web of Science ®Google Scholar
• Rollini F, Franchi F, Hu J, et al. Crushed prasugrel tablets in patients with STEMI undergoing primary percutaneous coronary intervention: the CRUSH study. J Am Coll Cardiol. 2016;67(17):1994–2004.
   PubMed Web of Science ®Google Scholar
• Niezgoda P, Sikora J, Barańska M, et al. Crushed sublingual versus oral ticagrelor administration strategies in patients with unstable angina. A pharmacokinetic/pharmacodynamic study. Thromb Haemost. 2017;117(4):718–726.
   PubMed Web of Science ®Google Scholar
• Vlachojannis GJ, Wilschut JM, Vogel RF, et al., Effect of prehospital crushed prasugrel tablets in patients with ST-Segment-Elevation Myocardial infarction planned for primary percutaneous coronary intervention: the randomized COMPARE CRUSH trial. Circulation. 2020;142(24): 2316–2328.
   PubMed Web of Science ®Google Scholar
• Asher E, Frydman S, Katz M, et al. For the PLATIS (Platelets and Thrombosis in Sheba) study group. Chewing versus swallowing ticagrelor to accelerate platelet inhibition in acute coronary syndrome - the CHEERS study. Thromb Haemost. 2017;117(4):727–733.
   PubMed Web of Science ®Google Scholar
• Asher E, Tal S, Mazin I, et al. Effect of chewing vs swallowing ticagrelor on platelet inhibition in patients with ST-segment elevation myocardial infarction: a randomized clinical trial. JAMA Cardiol. 2017;2(12):1380–1384.
   PubMed Web of Science ®Google Scholar
• Gargiulo G, Esposito G, Avvedimento M, et al. Cangrelor, Tirofiban, and Chewed or Standard Prasugrel regimens in patients With ST-segment-elevation Myocardial infarction: primary results of the FABOLUS-FASTER trial. Circulation. 2020;142(5):441–454.
   PubMed Web of Science ®Google Scholar
• Holm M, Tornvall P, Henareh L, et al. The MOVEMENT trial. J Am Heart Assoc. 2019;8(2):e010152.
   PubMed Web of Science ®Google Scholar
• Franchi F, Rollini F, Park Y, et al. Effects of Methylnaltrexone on Ticagrelor-induced Antiplatelet effects in coronary artery disease patients treated with morphine. JACC Cardiovasc Interv. 2019;12(16):1538–1549.
   PubMed Web of Science ®Google Scholar
• Sikora J, Niezgoda P, Baranska M, et al. Metoclopramide administration as a strategy to overcome Morphine-Ticagrelor interaction in patients with unstable Angina Pectoris—The METAMORPHOSIS trial. Thromb Haemost. 2018;118(12):2126–2133.
   PubMed Web of Science ®Google Scholar
• Saad M, Meyer-Saraei R, De Waha-thiele S, et al. Impact of morphine treatment with and without Metoclopramide Coadministration on Ticagrelor-Induced platelet inhibition in acute Myocardial Infarction: the Randomized MonAMI Trial. Circulation. 2020;141(16):1354–1356.
   PubMed Web of Science ®Google Scholar
• Capodanno D, Milluzzo RP, Angiolillo DJ. Intravenous antiplatelet therapies (glycoprotein IIb/IIIa receptor inhibitors and cangrelor) in percutaneous coronary intervention: from pharmacology to indications for clinical use. Ther Adv Cardiovasc Dis. 2019;13:1753944719893274.
   Google Scholar
• Tavenier AH, Hermanides RS, Fabris E, et al. Efficacy and safety of Glycoprotein IIb/IIIa Inhibitors on Top of Ticagrelor in STEMI: a subanalysis of the ATLANTIC Trial. Thromb Haemost. 2020;120(1):65–74.
   PubMed Web of Science ®Google Scholar
• Neumann FJ, Sousa-Uva M, Ahlsson A, et al. 2018 ESC/EACTS guidelines on myocardial revascularization. Eur Heart J. 2019;40:87–165.
   PubMed Web of Science ®Google Scholar
• Valgimigli M, Tebaldi M, Campo G, et al. Prasugrel versus tirofiban bolus with or without short post-bolus infusion with or without concomitant prasugrel administration in patients with myocardial infarction undergoing coronary stenting: the FABOLUS PRO (Facilitation through aggrastat by drOpping or shortening infusion line in patients with ST-segment elevation myocardial infarction compared to or on top of PRasugrel given at loading dOse) trial. JACC Cardiovasc Interv. 2012;5(3):268–277.
   PubMed Web of Science ®Google Scholar
• Siller-Matula JM, Specht S, Kubica J, et al. Abciximab as a bridging strategy to overcome morphine-prasugrel interaction in STEMI patients. Br J Clin Pharmacol. 2016;82(5):1343–1350.
   PubMed Web of Science ®Google Scholar
• Marian MJ, Abu Daya H, Chatterjee A, et al. Effects of crushed Ticagrelor Versus Eptifibatide bolus plus Clopidogrel in Troponin-Negative acute Coronary syndrome patients undergoing Percutaneous Coronary intervention: a randomized clinical trial. J Am Heart Assoc. 2019;8(23):e012844.
   PubMed Web of Science ®Google Scholar
• Ferreiro JL, Ueno M, Angiolillo DJ. Cangrelor: a review on its mechanism of action and clinical development. Expert Rev Cardiovasc Ther. 2009;7(10):1195–1201.
   PubMedGoogle Scholar
• Schneider DJ, Agarwal Z, Seecheran N, et al. Pharmacodynamic effects during the transition between cangrelor and ticagrelor. JACC Cardiovasc Interv. 2014;7(4):435–442.
   PubMed Web of Science ®Google Scholar
• Rollini F, Franchi F, Thano E, et al. In Vitro Pharmacodynamic Effects of Cangrelor on Platelet P2Y12 Receptor-Mediated Signaling in Ticagrelor-Treated Patients. JACC Cardiovasc Interv. 2017;10(13):1374–1375.
   PubMed Web of Science ®Google Scholar
• Rollini F, Franchi F, Tello-Montoliu A, et al. Pharmacodynamic effects of cangrelor on platelet P2Y12 receptor-mediated signaling in prasugrel-treated patients. JACC Cardiovasc Interv. 2014;7(4):426–434.
   PubMed Web of Science ®Google Scholar
• Angiolillo DJ, Schneider DJ, Bhatt DL, 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(1):44–55.
   PubMed Web of Science ®Google Scholar
• Bhatt DL, Stone GW, Mahaffey KW, et al. CHAMPION PHOENIX Investigators. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013;368(14):1303–1313.
   PubMed Web of Science ®Google Scholar
• Alexopoulos D, Pappas C, Sfantou D, et al. Cangrelor in Ticagrelor-Loaded STEMI Patients Undergoing Primary Percutaneous Coronary Intervention. J Am Coll Cardiol. 2018;72(14):1750–1751.
   PubMed Web of Science ®Google Scholar
• Franchi F, Rollini F, Rivas A, et al. Platelet inhibition with Cangrelor and Crushed Ticagrelor in patients with ST-Elevation Myocardial infarction undergoing primary percutaneous coronary intervention: results of the CANTIC study. Circulation. 2019;139(14):1661–1670.
   PubMed Web of Science ®Google Scholar
• Ubaid S, Ford TJ, Berry C, et al. Cangrelor versus Ticagrelor in patients treated with primary percutaneous coronary intervention: impact on platelet activity, myocardial microvascular function and infarct size: a randomized controlled trial. Thromb Haemost. 2019;119(7):1171–1181.
   PubMed Web of Science ®Google Scholar
• Mangiacapra F, Barbato E, Patti G, et al. Point-of-care assessment of platelet reactivity after clopidogrel to predict myonecrosis in patients undergoing percutaneous coronary intervention. JACC Cardiovasc Interv. 2010;3(3):318–323.
   PubMed Web of Science ®Google Scholar
• Capranzano P, Capodanno D, Bucciarelli-Ducci C, et al. Impact of residual platelet reactivity on reperfusion in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Eur Heart J Acute Cardiovasc Care. 2016;5(5):475–486.
   PubMed Web of Science ®Google Scholar
• Roule V, Heudel T, Lemaitre A, et al. Residual platelet reactivity after pre-treatment with ticagrelor prior to primary percutaneous coronary intervention is associated with suboptimal myocardial reperfusion. Eur Heart J Acute Cardiovasc Care. 2019 Aug 12; Online ahead of print.
   Google Scholar
• Aitmokhtar O, Paganelli F, Benamara S, et al. Impact of platelet inhibition level on subsequent no-reflow in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Arch Cardiovasc Dis. 2017;110(11):626–633.
   PubMed Web of Science ®Google Scholar
• Morishima I, Sone T, Okumura K, et al. Angiographic no-reflow phenomen as a predictor of adverse long-term outcome in patients treated with percutaneous transluminal coronary angioplasty for first acute myocardial infarction. J Am Coll Cardiol. 2000;36(4):1202–1209.
   PubMed Web of Science ®Google Scholar
• Silvain J, Zeitouni M, Paradies V, et al. Cardiac procedural myocardial injury, infarction, and mortality in patients undergoing elective percutaneous coronary intervention: a pooled analysis of patient-level data. Eur Heart J. 2021;42(4):323–334.
   PubMed Web of Science ®Google Scholar
• Généreux P, Stone GW, Harrington RA, et al. Impact of intraprocedural stent thrombosis during percutaneous coronary intervention: insights from the CHAMPION PHOENIX trial (Clinical trial comparing cangrelor to clopidogrel standard of care therapy in subjects who require percutaneous coronary intervention). J Am Coll Cardiol. 2014;63(7):619–629.
   PubMed Web of Science ®Google Scholar
• Iglesias JF, Valgimigli M, Carbone F, et al. Effects of Fentanyl Versus Morphine on Ticagrelor-Induced Platelet Inhibition in Patients With ST-Segment Elevation Myocardial Infarction: the PERSEUS randomized trial. Circulation. 2020;142(25):2479–2481.
   PubMed Web of Science ®Google Scholar
• Furtado RHM, Nicolau JC, Guo J, et al. Morphine and cardiovascular outcomes among patients with Non-ST-Segment elevation acute coronary syndromes undergoing coronary angiography. J Am Coll Cardiol. 2020;75(3):289–300.
   PubMed Web of Science ®Google Scholar
• Batchelor R, Liu DH, Bloom J, et al. Association of periprocedural intravenous morphine use on clinical outcomes in ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention: systematic review and meta-analysis. Catheter Cardiovasc Interv. 2020;96(1):76–88.
   PubMed Web of Science ®Google Scholar
• Ibanez B, James S, Agewall S, et al. 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):119–177.
   PubMed Web of Science ®Google Scholar
• Tavenier AH, Hermanides RS, Ottervanger JP, et al. Impact of opioids on P2Y12-receptor inhibition in patients with ST-elevation myocardial infarction who are pre-treated with crushed ticagrelor: opioids aNd crushed Ticagrelor in Myocardial infarction Evaluation (ON-TIME 3) trial [published,]. Eur Heart J Cardiovasc Pharmacother. 2020; Jul 30 Online ahead of print. Doi: https://doi.org/10.1093/ehjcvp/pvaa095.
   Google Scholar
• Koul S, Smith JG, Götberg M, et al. No benefit of ticagrelor pretreatment compared with treatment during percutaneous coronary intervention in patients with ST-Segment-Elevation Myocardial infarction undergoing primary percutaneous coronary intervention. Circ Cardiovasc Interv. 2018;11(3):e005528.
   PubMed Web of Science ®Google Scholar
• Zwart B, Yazdani M, Ow KW, et al. Use of glycoprotein IIb/IIIa antagonists to prevent stent thrombosis in morphine-treated patients with ST-elevation myocardial infarction. Platelets. 2020;31(2):174–178.
   PubMed Web of Science ®Google Scholar
• Groves EM, Bhatt DL, Steg PG, et al. Incidence, predictors, and outcomes of acquired Thrombocytopenia after percutaneous coronary intervention: a Pooled, Patient-Level analysis of the CHAMPION trials (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition). Circ Cardiovasc Interv. 2018;11(4):e005635.
   PubMed Web of Science ®Google Scholar
• Vaduganathan M, Harrington RA, Stone GW, et al. Cangrelor with and without Glycoprotein IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention. J Am Coll Cardiol. 2017;69:176–185.
   PubMedGoogle Scholar
• Angiolillo DJ, Bhatt DL, Steg PG, et al. Impact of cangrelor overdosing on bleeding complications in patients undergoing percutaneous coronary intervention: insights from the CHAMPION trials. J Thromb Thrombolysis. 2015;40(3):317–322.
   PubMed Web of Science ®Google Scholar
• Franchi F, Rollini F, Park Y, et al. A safety evaluation of cangrelor in patients undergoing PCI. Expert Opin Drug Saf. 2016;15(2):275–285.
   PubMed Web of Science ®Google Scholar
• Vaduganathan M, Harrington RA, Stone GW, et al. Evaluation of Ischemic and bleeding risks associated with 2 parenteral antiplatelet strategies comparing cangrelor with Glycoprotein IIb/IIIa Inhibitors: an exploratory analysis from the CHAMPION trials. JAMA Cardiol. 2017;2(2):127–135.
   PubMed Web of Science ®Google Scholar
• Angiolillo DJ, Rollini F, Storey RF, et al., International expert consensus on switching platelet P2Y12 Receptor–Inhibiting Therapies. Circulation. 2017;136(20): 1955–1975. .
   PubMed Web of Science ®Google Scholar
• Van’t Hof AW, Ten BJ, Heestermans T, et al. Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial. Lancet. 2008;372(9638):537–546.
   PubMed Web of Science ®Google Scholar
• Montalescot G, Borentain M, Payot L, et al. Early vs late administration of glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention of acute ST-segment elevation myocardial infarction: a meta-analysis. JAMA. 2004;292(3):362–366.
   PubMed Web of Science ®Google Scholar
• Aparna A, Kumar YS, Bhikshapathi DVRN. Formulation and in vivo evaluation of Ticagrelor self- nanoemulsifying drug delivery systems. Pharm Nanotechnol. 2021;9(1):61-69.
   Google Scholar
• Kim SJ, Lee HK, Na YG, et al. A novel composition of ticagrelor by solid dispersion technique for increasing solubility and intestinal permeability. Int J Pharm. 2019;555:11–18.
   PubMed Web of Science ®Google Scholar
• Milluzzo RP, Franchina GA, Capodanno D, et al. Selatogrel, a novel P2Y12 inhibitor: a review of the pharmacology and clinical development. Expert Opin Investig Drugs. 2020;29(6):537–546.
   PubMed Web of Science ®Google Scholar
• Sinnaeve P, Fahrni G, Schelfaut D, et al. Subcutaneous Selatogrel inhibits platelet aggregation in patients with acute myocardial infarction. J Am Coll Cardiol. 2020;75(20):2588–2597.
   PubMed Web of Science ®Google Scholar