What are glycoprotein IIb/IIIa inhibitors?

Glycoprotein IIb/IIIa Inhibitors

Glycoprotein IIb/IIIa inhibitors are parenterally administered drugs that block platelet aggregation by preventing platelet cross-linking via fibrinogen or von Willebrand factor binding to the glycoprotein IIb/IIIa receptor, primarily used as adjunctive therapy during percutaneous coronary intervention (PCI) in patients with large thrombus burden or as rescue therapy for PCI complications. 1

Mechanism of Action

• Glycoprotein IIb/IIIa inhibitors block the common pathway for platelet aggregation by occupying platelet receptors, preventing platelet-to-platelet crosslinking by fibrinogen 1
• This action promotes stabilization of ruptured plaque and passivates the epithelium, decreasing further adverse cardiac events 1
• By inhibiting platelet aggregation, these drugs prevent thrombus formation during PCI, attenuating or preventing acute coronary occlusion and embolization of microthrombi to the distal microvasculature 1, 2

Available Agents

• Currently, three glycoprotein IIb/IIIa inhibitors are commercially available for intravenous administration 1, 2:
  • Abciximab
  • Tirofiban
  • Eptifibatide
• All require a 24- to 72-hour infusion to show clinical benefit 1
• These agents differ in their pharmacological properties but share the same mechanism of action by targeting the glycoprotein IIb/IIIa platelet receptor 2, 3

Current Clinical Indications

• Primary indication: Adjunctive use during PCI in patients with large thrombus burden, no-reflow, or slow flow to improve procedural success and reduce infarct size 1
• Not recommended: Routine administration in patients with acute coronary syndrome (ACS) due to lack of ischemic benefit and increased risk of bleeding 1
• These agents were first evaluated before contemporary antiplatelet and interventional strategies were introduced and in an era when time to coronary revascularization was substantially longer than today 1
• Limited data are available for glycoprotein IIb/IIIa inhibitors in patients receiving more potent P2Y12 inhibitors and earlier PCI with contemporary drug-eluting stents 1

Specific Clinical Scenarios

• High-risk PCI: Reasonable to use in patients with positive troponin or ischemic ST-segment depression when early interventional strategy is anticipated 1
• Timing considerations: Greatest benefit observed when treatment is initiated within 6 hours of symptom onset and in patients with anticipated delay in PCI 1
• Non-interventional strategy: May be considered in high-risk patients (positive troponin or ischemic ST-segment depression) managed conservatively 1
• Rescue therapy: Used as "bailout" therapy in patients with PCI complications such as no-reflow or persistent/recurring thrombus at the lesion 1, 4

Safety Considerations

• Bleeding risk: Administration is associated with an increase in major and minor bleeding, particularly at arterial access sites for cardiac catheterization or from gastrointestinal/genitourinary tracts 5
• Thrombocytopenia: Acute, profound thrombocytopenia (immune-mediated and non-immune mediated) has been reported; monitoring platelet counts is recommended 5
• Risk factors for bleeding: Older age, history of bleeding disorders, and concomitant use of drugs that increase bleeding risk (thrombolytics, oral anticoagulants, NSAIDs, P2Y12 inhibitors) 5
• Contraindications 5:
  • History of bleeding diathesis or active abnormal bleeding within previous 30 days
  • Severe uncontrolled hypertension
  • Major surgery within preceding 6 weeks
  • History of stroke within 30 days or any history of hemorrhagic stroke
  • Current/planned administration of another parenteral GP IIb/IIIa inhibitor
  • Dependency on renal dialysis
  • Hypersensitivity to the agent or any component

Evolution of Clinical Use

• The role of glycoprotein IIb/IIIa inhibitors has evolved significantly over time 2, 3
• In the contemporary era of more potent oral P2Y12 inhibitors (prasugrel, ticagrelor) and safer anticoagulants (bivalirudin), their use has become more selective 6, 4
• Current niche includes patients requiring emergent PCI before oral agents are fully active and unstable patients requiring transport to PCI centers, particularly those likely to have intracoronary thrombus 7
• The intravenous route provides effectiveness in patients with difficulties in drug intake or impaired absorption of oral medications 3

Administration Considerations

• Dosing is weight-based and requires careful calculation to avoid dosing errors 5
• In patients undergoing PCI, infusion should be continued until hospital discharge or up to 18-24 hours, whichever comes first 5
• Early arterial sheath removal is encouraged while the agent is being infused, with specific protocols for heparin discontinuation and monitoring of coagulation parameters 5
• Both the glycoprotein IIb/IIIa inhibitor and heparin should be discontinued with sheath hemostasis achieved at least 2-4 hours before hospital discharge 5