Unstable angina non ST elevation myocardial infarction GPIIb/IIIa inhibitor
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-in-Chief: Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.; Smita Kohli, M.D.
Overview
Glycoprotein IIb/IIIa (Gp IIb/IIIa) is an integrin complex present on the surface of the platelets. This complex aids in platelet aggregation during the clotting process by acting as a receptor for fibrinogen. Gp IIb/IIIa inhibitors are a class of antiplatelet agents that prevent platelet aggregation and thrombus formation by inhibiting the integrin complex.
Glycoprotein IIb/IIIa Inhibitors in the Management of Unstable Angina/NSTEMI
Three agents currently available are abciximab, eptifibatide and tirofiban, all three of which are now included by the ACC/AHA guidelines for use in PCI.
Mechanism of Action
- GP IIb/IIIa inhibitors inhibit the fibrinogen-mediated cross linkage of platelets, which is the final common pathway of platelet aggregation.
Clinical Trial Data
- ISAR-REACT 2 trial[1] studied abciximab in NSTEMI patients. This was a multicenter, randomized, double-blind, placebo-controlled study enrolling 2022 patients with non-ST-segment elevation ACS undergoing PCI. Results showed that abciximab reduces the risk of adverse events in patients with non-ST-segment elevation ACS undergoing PCI after pretreatment with 600 mg of clopidogrel.
- Most recently, the EARLY ACS trial[2] revealed that in patients who had acute coronary syndromes without ST-segment elevation, the use of eptifibatide 12 hours or more before angiography was not superior to the provisional use of eptifibatide after angiography. The early use of eptifibatide was associated with an increased risk of non-life threatening bleeding and need for transfusion. Potential benefit with this class of drugs also led to study of oral GP IIa/IIIb inhibitors.
- A major study involving Orbofiban (an oral GP IIb/IIIa inhibitor) failed to demonstrate improved outcomes and was associated with increased mortality.[3]
Indications
- The benefits provided by abciximab appear to be confined to patients presenting with an elevated troponin level.
- The benefit of GP IIb/IIIa inhibition appears greater when used in high-risk patients and in those with ST segment changes.
- The benefit was also seen in high risk patients with or without revascularization.
Contraindications
- Abciximab is not recommended if PCI is not planned. Eptifibatide and tirofiban are preferred agents when delay in coronary angiography and PCI is anticipated.
Dosing
- All three agents are for intravenous usage and are given by bolus and continuous infusion.
- Optimal timing of GP IIb/IIIa inhibition remains controversial with no clear data available from current trials. More so, most of the trials related to timing of GP IIa/IIIb inhibitors involve patients with STEMI and hence cannot be applied to all ACS patients.
Disadvantages
- A major side effect of GP IIb/IIIa inhibitors is thrombocytopenia and hence increased bleeding. Therefore, platelet monitoring is indicated during its use.
2011 ACCF/AHA/SCAI Guidelines for Percutaneous Coronary Intervention (DO NOT EDIT)[4]
Intravenous Antiplatelet Therapy in Unstable Angina/Non-ST Elevation Myocardial Infarction (UA/NSTEMI) (DO NOT EDIT)[4]
| Class I |
| "1. In UA/NSTEMI patients with high-risk features (e.g., elevated troponin level) not treated with bivalirudin and not adequately pre-treated with clopidogrel, it is useful at the time of PCI to administer a GP IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-bolus dose tirofiban) in patients treated with unfractionated heparin therapy (UFH).[5][6][7][8][9][10] (Level of Evidence: A)" |
| Class IIa |
| "1. In UA/NSTEMI patients with high-risk features (e.g., elevated troponin level) treated with unfractionated heparin therapy (UFH)and adequately pretreated with clopidogrel, it is reasonable at the time of PCI to administer a GP IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-bolus dose tirofiban).[8][11] (Level of Evidence: B)" |
References
- ↑ Kastrati A, Mehilli J, Neumann FJ; et al. (2006). "Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial". JAMA. 295 (13): 1531–8. doi:10.1001/jama.295.13.joc60034. PMID 16533938. Unknown parameter
|month=ignored (help) - ↑ Giugliano RP, White JA, Bode C; et al. (2009). "Early versus delayed, provisional eptifibatide in acute coronary syndromes". N. Engl. J. Med. 360 (21): 2176–90. doi:10.1056/NEJMoa0901316. PMID 19332455. Unknown parameter
|month=ignored (help) - ↑ Cannon CP, McCabe CH, Wilcox RG; et al. (2000). "Oral glycoprotein IIb/IIIa inhibition with orbofiban in patients with unstable coronary syndromes (OPUS-TIMI 16) trial". Circulation. 102 (2): 149–56. PMID 10889124. Unknown parameter
|month=ignored (help) - ↑ 4.0 4.1 Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, Chambers CE, Ellis SG, Guyton RA, Hollenberg SM, Khot UN, Lange RA, Mauri L, Mehran R, Moussa ID, Mukherjee D, Nallamothu BK, Ting HH (2011). "2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: Executive Summary A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions" (PDF). Journal of the American College of Cardiology. 58 (24): 2550–83. doi:10.1016/j.jacc.2011.08.006. PMID 22070837. Retrieved 2011-12-08. Text "PDF" ignored (help); Unknown parameter
|month=ignored (help) - ↑ "Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. The EPILOG Investigators". The New England Journal of Medicine. 336 (24): 1689–96. 1997. doi:10.1056/NEJM199706123362401. PMID 9182212. Retrieved 2011-12-15. Unknown parameter
|month=ignored (help) - ↑ Boersma E, Akkerhuis KM, Théroux P, Califf RM, Topol EJ, Simoons ML (1999). "Platelet glycoprotein IIb/IIIa receptor inhibition in non-ST-elevation acute coronary syndromes: early benefit during medical treatment only, with additional protection during percutaneous coronary intervention". Circulation. 100 (20): 2045–8. PMID 10562258. Retrieved 2011-12-15. Unknown parameter
|month=ignored (help) - ↑ Hamm CW, Heeschen C, Goldmann B, Vahanian A, Adgey J, Miguel CM, Rutsch W, Berger J, Kootstra J, Simoons ML (1999). "Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels. c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) Study Investigators". The New England Journal of Medicine. 340 (21): 1623–9. doi:10.1056/NEJM199905273402103. PMID 10341274. Retrieved 2011-12-15. Unknown parameter
|month=ignored (help) - ↑ 8.0 8.1 Sosnowski C (2006). "[Commentary to the article: Kastrati A, Mehilli J, Neumann FJ, et al. Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial. JAMA 2006; 295: 1531-8]". Kardiologia Polska (in Polish). 64 (8): 913–6, discussion 917–8. PMID 16981067. Retrieved 2011-12-15. Unknown parameter
|month=ignored (help) - ↑ Roffi M, Chew DP, Mukherjee D, Bhatt DL, White JA, Heeschen C, Hamm CW, Moliterno DJ, Califf RM, White HD, Kleiman NS, Théroux P, Topol EJ (2001). "Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndromes". Circulation. 104 (23): 2767–71. PMID 11733392. Retrieved 2011-12-15. Unknown parameter
|month=ignored (help) - ↑ "Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. The EPIC Investigation". The New England Journal of Medicine. 330 (14): 956–61. 1994. doi:10.1056/NEJM199404073301402. PMID 8121459. Retrieved 2011-12-15. Unknown parameter
|month=ignored (help) - ↑ Valgimigli M, Percoco G, Barbieri D, Ferrari F, Guardigli G, Parrinello G, Soukhomovskaia O, Ferrari R (2004). "The additive value of tirofiban administered with the high-dose bolus in the prevention of ischemic complications during high-risk coronary angioplasty: the ADVANCE Trial". Journal of the American College of Cardiology. 44 (1): 14–9. doi:10.1016/j.jacc.2004.03.042. PMID 15234398. Retrieved 2011-12-15. Unknown parameter
|month=ignored (help)
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