The role of platelet glycoprotein IIb / IIIa inhibitors in current treatment of acute coronary syndrome

Current management of patients with acute coronary syndrome (ACS) includes a dual antiplatelet therapy with acetylsalicylic acid and a platelet P2Y12 receptor inhibitor. For patients without a high risk of bleeding, prasugrel and ticagrelor are preferred, since their effect is more pronounced, less dependent on metabolism of a specific patient, and occurs faster that the effect of clopidogrel. The prescription rate of platelet glycoprotein IIb/IIIa (GP IIb / IIIa) receptor inhibitors has considerably decreased. However, these drugs remain relevant in percutaneous coronary interventions in patients with a high risk of coronary thrombosis or a massive coronary thrombus, in thrombotic complications of the procedure, and in the “no-reflow” phenomenon. The intravenous route of GP IIb / IIIa inhibitor administration provides their effectiveness in patients with difficulties of drug intake or with impaired absorption of oral medications. This review presents clinical and pharmacological characteristics of various GP IIb / IIIa inhibitors and data of randomized clinical studies and registries of recent years that evaluated results of their use in patients with ACS.

1. 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. Therapeutic Advances in Cardiovascular Disease. 2019;13:175394471989327. DOI: 10.1177/1753944719893274

2. Centurión OA. Current Role of Platelet Glycoprotein IIb/IIIa Inhibition in the Therapeutic Management of Acute Coronary Syndromes in the Stent Era. Journal of Cardiology & Current Research. 2016;5(4):1–11. DOI: 10.15406/jccr.2016.05.00175

3. Safley DM, Venkitachalam L, Kennedy KF, Cohen DJ. Impact of Glycoprotein IIb/IIIa Inhibition in Contemporary Percutaneous Coronary Intervention for Acute Coronary Syndromes. JACC: Cardiovascular Interventions. 2015;8(12):1574–82. DOI: 10.1016/j.jcin.2015.04.031

4. Sethi A, Bajaj A, Bahekar A, Bhuriya R, Singh M, Ahmed A et al. Glycoprotein IIb/IIIa inhibitors with or without thienopyridine pretreatment improve outcomes after primary percutaneous coronary intervention in high-risk patients with ST elevation myocardial infarctiona meta-regression of randomized controlled trials. Catheterization and Cardiovascular Interventions. 2013;82(2):171–81. DOI: 10.1002/ccd.24653

5. Collet J-P, Thiele H, Barbato E, Barthélémy O, Bauersachs J, Bhatt DL et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. European Heart Journal. 2021;42(14):1289–367. DOI: 10.1093/eurheartj/ehaa575

6. Staroverov I.I., Shakhnovich R.M., Gilyarov M.Yu., Komarov A.L., Konstantinova E.V., Panchenko E.P. et al. Eurasian clinical guidelines on diagnosis and treatment of acute coronary syndrome with st segment elevation (STEMI). Eurasian heart journal. 2020;1(30):4–77. DOI: 10.38109/2225-1685-2020-1-4-77

7. Tummala R, Rai MP. Glycoprotein IIb/IIIa Inhibitors. [PMID: 32119263]. In: StatPearls-Treasure Island (FL): StatPearls Publishing;2022.

8. Orzalkiewicz M, Hodson J, Kwok CS, Ludman PF, Giblett JP, George S et al. Comparison of Routine Versus Selective Glycoprotein IIb/IIIa Inhibitors Usage in Primary Percutaneous Coronary Intervention (from the British Cardiovascular Interventional Society). The American Journal of Cardiology. 2019;124(3):373–80. DOI: 10.1016/j.amjcard.2019.05.010

9. Schneider DJ. Anti-platelet therapy: glycoprotein IIb-IIIa antagonists: Glycoprotein IIb-IIIa antagonists. British Journal of Clinical Pharmacology. 2011;72(4):672–82. DOI: 10.1111/j.1365-2125.2010.03879.x

10. Mazurov A.V. Glycopritein IIb/IIIa antagonists in acute coronary syndrome. Current questions of heart and vascular diseases. 2008;4:24–30.

11. Mazurov AV, Pevzner DV, Antonova OA, Byzova TV, Khaspekova SG, Semenov AV et al. Safety, inhibition of platelet aggregation and pharmacokinetics of F(ab′) 2 fragments of the anti-glycoprotein IIb-IIIa monoclonal antibody FRaMon in highrisk coronary angioplasty. Platelets. 2002;13(8):465–77. DOI: 10.1080/0953710021000057839

12. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H 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). European Heart Journal. 2018;39(2):119–77. DOI: 10.1093/eurheartj/ehx393

13. Zeymer U, Margenet A, Haude M, Bode C, Lablanche J-M, Heuer H et al. Randomized Comparison of Eptifibatide Versus Abciximab in Primary Percutaneous Coronary Intervention in Patients With Acute ST-Segment Elevation Myocardial Infarction. Journal of the American College of Cardiology. 2010;56(6):463–9. DOI: 10.1016/j.jacc.2009.08.093

14. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) Trial Investigators. Inhibition of Platelet Glycoprotein IIb/IIIa with Eptifibatide in Patients with Acute Coronary Syndromes. New England Journal of Medicine. 1998;339(7):436–43. DOI: 10.1056/NEJM199808133390704

15. Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISMPLUS) Study Investigators. Inhibition of the Platelet Glycoprotein IIb/IIIa Receptor with Tirofiban in Unstable Angina and Non–Q-Wave Myocardial Infarction. New England Journal of Medicine. 1998;338(21):1488–97. DOI: 10.1056/NEJM199805213382102

16. Topol EricJ, Califf RobertM, Weisman HarlanF, Ellis StephenG, Tcheng JamesE, Worley S et al. Randomised trial of coronary intervention with antibody against platelet IIb/IIIa iritegrin for reduction of clinical restenosis: results at six months. The Lancet. 1994;343(8902):881–6. DOI: 10.1016/S0140-6736(94)90007-8

17. De Luca G, Suryapranata H, Stone GW, Antoniucci D, Tcheng JE, Neumann F-J et al. Abciximab as Adjunctive Therapy to Reperfusion in Acute ST-Segment Elevation Myocardial Infarction: A Meta-analysis of Randomized Trials. JAMA. 2005;293(14):1759–65. DOI: 10.1001/jama.293.14.1759

18. Montalescot G, Antoniucci D, Kastrati A, Neumann FJ, Borentain M, Migliorini A et al. Abciximab in primary coronary stenting of ST-elevation myocardial infarction: a European meta-analysis on individual patients’ data with long-term follow-up. European Heart Journal. 2007;28(4):443–9. DOI: 10.1093/eurheartj/ehl472

19. Gurm HS, Tamhane U, Meier P, Grossman PM, Chetcuti S, Bates ER. A Comparison of Abciximab and Small-Molecule Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing Primary Percutaneous Coronary Intervention: A Meta-Analysis of Contemporary Randomized Controlled Trials. Circulation: Cardiovascular Interventions. 2009;2(3):230–6. DOI: 10.1161/CIRCINTERVENTIONS.108.847996

20. Ottani F, La Vecchia L, De Vita M, Catapano O, Tarantino F, Galvani M. Comparison by Meta-Analysis of Eptifibatide and Tirofiban to Abciximab in Patients With ST-Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention. The American Journal of Cardiology. 2010;106(2):167-174.e1. DOI: 10.1016/j.amjcard.2010.03.012

21. Simoons ML, GUSTO IV-ACS Investigators. Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularisation: the GUSTO IV-ACS randomised trial. The Lancet. 2001;357(9272):1915–24. DOI: 10.1016/S0140-6736(00)05060-1

22. Beavers CJ, Jennings DL. Use of Glycoprotein IIb/IIIa Inhibitors in the Modern Era of Acute Coronary Syndrome Management: A Survey of Cardiovascular Clinical Pharmacists. Journal of Pharmacy Practice. 2021;34(3):372–7. DOI: 10.1177/0897190019872386

23. Montalescot G, van ’t Hof AW, Lapostolle F, Silvain J, Lassen JF, Bolognese L et al. Prehospital Ticagrelor in ST-Segment Elevation Myocardial Infarction. New England Journal of Medicine. 2014;371(11):1016–27. DOI: 10.1056/NEJMoa1407024

24. de Waha S, Eitel I, Desch S, Fuernau G, Lurz P, Urban D et al. Intravenous morphine administration and reperfusion success in ST-elevation myocardial infarction: insights from cardiac magnetic resonance imaging. Clinical Research in Cardiology. 2015;104(9):727–34. DOI: 10.1007/s00392-015-0835-2

25. Zwart B, Yazdani M, Ow KW, Richardson JD, Iqbal J, Gunn JP 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):174–8. DOI: 10.1080/09537104.2019.1665642

26. Saleiro C, Teixeira R, De Campos D, Lopes J, Oliveiros B, Costa M et al. Glycoprotein IIb/IIIa inhibitors for cardiogenic shock complicating acute myocardial infarction: a systematic review, meta-analysis, and meta-regression. Journal of Intensive Care. 2020;8(1):85. DOI: 10.1186/s40560-020-00502-y

27. De Felice F, Tomassini F, Fiorilli R, Gagnor A, Parma A, Cerrato E et al. Effect of Abciximab Therapy in Patients Undergoing Coronary Angioplasty for Acute ST-Elevation Myocardial Infarction Complicated by Cardiogenic Shock. Circulation Journal. 2015;79(7):1568–74. DOI: 10.1253/circj.CJ-15-0053

28. Blanchart K, Heudel T, Ardouin P, Lemaitre A, Briet C, Bignon M et al. Glycoprotein IIb/IIIa inhibitors use in the setting of primary percutaneous coronary intervention for ST elevation myocardial infarction in patients pre‐treated with newer P2Y12 inhibitors. Clinical Cardiology. 2021;44(8):1080–8. DOI: 10.1002/clc.23654

29. Erlikh A.D., Gratsiansky N.A. Registry of Acute Coronary Syndromes ‘RECORD-3’. Characteristics of Patients and Treatment During Initial Hospitalization. Kardiologiia. 2016;56(4):16–24. DOI: 10.18565/cardio.2016.4.16-24