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An Updated Review on Glycoprotein IIb/IIIa Inhibitors as Antiplatelet Agents: Basic and Clinical Perspectives

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Abstract

The glycoprotein (GP) IIb/IIIa receptor is found integrin present in platelet aggregations. GP IIb/IIIa antagonists interfere with platelet cross-linking and platelet-derived thrombus formation through the competition with fibrinogen and von Willebrand factor. Currently, three parenteral GP IIb/IIIa competitors (tirofiban, eptifibatide, and abciximab) are approved for clinical use in patients affected by percutaneous coronary interventions (PCI) in the location of acute coronary syndrome (ACS). GP IIb/IIIa antagonists have their mechanism of action in platelet aggregation prevention, distal thromboembolism, and thrombus formation, whereas the initial platelet binding to damage vascular areas is preserved. This work is aimed to provide a comprehensive review of the significance of GP IIb/IIIa inhibitors as a sort of antiplatelet agent. Their mechanism of action is based on factors that affect their efficacy. On the other hand, drugs that inhibit GP IIb/IIIa already approved by the FDA were reviewed in detail. Results from major clinical trials and regulatory practices and guidelines to deal with GP IIb/IIIa inhibitors were deeply investigated. The cardiovascular pathology and neuro-interventional surgical application of GP IIb/IIIa inhibitors as a class of antiplatelet agents were developed in detail. The therapeutic risk/benefit balance of currently available GP IIb/IIa receptor antagonists is not yet well elucidated in patients with ACS who are not clinically evaluated regularly for early cardiovascular revascularization. On the other hand, in patients who have benefited from PCI, the antiplatelet therapy intensification by the addition of a GP IIb/IIIa receptor antagonist (intravenously) may be an appropriate therapeutic strategy in reducing the occurrence of risks of thrombotic complications related to the intervention. Development of GP IIb/IIIa inhibitors with oral administration has the potential to include short-term antiplatelet benefits compared with intravenous GP IIb/IIIa inhibitors for long-term secondary preventive therapy in cardiovascular disease. But studies showed that long-term oral administration of GP IIb/IIIa receptor inhibitors has been ineffective in preventing ischemic events. Paradoxically, they have been linked to a high risk of side effects by producing prothrombotic and pro-inflammatory events.

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Acknowledgments

MM wants to thank ANID FONDECYT Iniciación 11190641 and ANID CENTROS BASALES ACE210012.

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Authors and Affiliations

  1. Facultad de Medicina, Universidad del Azuay, Cuenca, Ecuador

    Javad Sharifi-Rad

  2. V.I. Nikitin Chemistry Institute of the National Academy of Sciences of Tajikistan, Ayni 299/2, 734063, Dushanbe, Tajikistan

    Farukh Sharopov

  3. Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt

    Shahira M. Ezzat

  4. Department of Pharmacognosy, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), 6th October, 12566, Egypt

    Shahira M. Ezzat

  5. Department of Analytical and Food Chemistry, Faculty of Pharmacy, Al-Andalus University for Medical Sciences, 35XQ+C2F, Tartous, Syria

    Wissam Zam

  6. Functional Foods, Nutraceuticals and Phytomedicine Unit, Department of Biochemistry, Federal University of Technology, Akure, Akure, 340252, Nigeria

    Adedayo Oluwaseun Ademiluyi

  7. Department of Biochemistry, Federal University, Oye-Ekiti, Oye-Ekiti, 371104, Nigeria

    Olubukola Helen Oyeniran

  8. Microbiology, Biotechnology and Nanotechnology Laboratory, Department of Microbiology, Edo University Iyamho, Iyamho, Edo, Nigeria

    Olubukola Helen Oyeniran & Charles Oluwaseun Adetunji

  9. Department of Anatomy, College of Basic Medical Science, Edo University Iyamho, Iyamho, Nigeria

    Osahon Itohan Roli

  10. Institute for Medicinal Plants Research “Dr. Josif Pančić”, Tadeuša Košćuška 1, 11000, Belgrade, Serbia

    Jelena Živković

  11. Department of Nutrition and Dietetics, Faculty of Pharmacy, and Centre for Healthy Living, University of Concepción, 4070386, Concepción, Chile

    Miquel Martorell

  12. Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania

    Anca Oana Docea

  13. Laboratory of Histology, Embryology, and Cytogenetic, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, 10100, Rabat, Morocco

    Nasreddine El Omari

  14. Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat, Morocco

    Abdelhakim Bouyahya

  15. Centro Tecnológico de la Carne de Galicia, Rúa Galicia Nº 4, Parque Tecnológico de Galicia, 32900, San Cibrao das Vinas, Spain

    José M. Lorenzo

  16. Facultade de Ciencias, Área de Tecnoloxía dos Alimentos, Universidade de Vigo, 32004, Ourense, Spain

    José M. Lorenzo

  17. Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania

    Daniela Calina

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  1. Javad Sharifi-Rad
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Sharifi-Rad, J., Sharopov, F., Ezzat, S.M. et al. An Updated Review on Glycoprotein IIb/IIIa Inhibitors as Antiplatelet Agents: Basic and Clinical Perspectives. High Blood Press Cardiovasc Prev 30, 93–107 (2023). https://doi.org/10.1007/s40292-023-00562-9

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