Glycoprotein IIb IIIa Inhibitors

Glycoprotein IIb/IIIa inhibitors block the final common pathway of platelet aggregation, the binding of fibrinogen to the activated IIb/IIIa receptor. They are the most potent antiplatelet drugs but carry the highest bleeding risk. They are given intravenously for short periods around percutaneous coronary intervention, and routine upstream use is no longer advised.

Members. Abciximab (monoclonal antibody Fab fragment), eptifibatide (cyclic heptapeptide) and tirofiban (non-peptide).

Mechanism. Each drug occupies the IIb/IIIa receptor, preventing fibrinogen and von Willebrand factor cross-linking of platelets. Abciximab binds with high affinity and dissociates slowly. Eptifibatide and tirofiban bind reversibly and dissociate within hours.

Pharmacokinetics. Abciximab has a plasma half-life of under 30 minutes, but platelet-bound drug keeps platelet function suppressed for 24 to 48 hours. Eptifibatide and tirofiban have a half-life of about 2 hours, with platelet function recovering 4 to 8 hours after stopping. Both are cleared mainly by the kidney.

• Abciximab: long platelet effect; used only for primary percutaneous coronary intervention; supply limited in many regions.
• Eptifibatide: short effect; non-ST-elevation acute coronary syndrome and percutaneous coronary intervention; renal dose adjustment.
• Tirofiban: short effect; similar use; renal dose adjustment.

• Bailout in percutaneous coronary intervention: for large thrombus burden, no-reflow, slow flow, or thrombotic complications during stenting.
• Eptifibatide: 180 micrograms/kg bolus, a second bolus after 10 minutes in percutaneous coronary intervention, then infusion 2 micrograms/kg/minute for up to 18 to 24 hours. Reduce infusion to 1 microgram/kg/minute if creatinine clearance is 30 to 50 mL/min, and avoid below 30 mL/min.
• Tirofiban: 25 micrograms/kg bolus then 0.15 micrograms/kg/minute for up to 18 hours. Halve the dose if creatinine clearance is under 60 mL/min (30 mL/min in some labels).
• Abciximab: 0.25 mg/kg bolus then 0.125 micrograms/kg/minute (maximum 10 micrograms/minute) for 12 hours.
• Heparin dose with a glycoprotein IIb/IIIa inhibitor: reduce unfractionated heparin to 50 to 70 units/kg bolus in percutaneous coronary intervention, targeting an activated clotting time of 200 to 250 seconds.
• Selection: use in selected high-risk percutaneous coronary intervention with a plan for early cessation. Not routine in low-risk patients or with bivalirudin-based regimens.

Contraindications. Active bleeding, recent major surgery or trauma, history of intracranial haemorrhage, stroke within 30 days, severe uncontrolled hypertension, platelet count under 100 x 10^9/L, severe renal failure (eptifibatide), and previous thrombocytopenia from the same drug.

Adverse effects. Bleeding (access site, gastrointestinal, intracranial), thrombocytopenia (severe in up to 1% to 2%, with delayed onset or after re-exposure with abciximab), and hypersensitivity (abciximab).

Interactions. Heparin, warfarin, thrombolytics, NSAIDs and other antiplatelet drugs raise bleeding. Avoid concurrent use of other glycoprotein IIb/IIIa inhibitors.

Monitoring. Platelet count and haemoglobin before starting, at 2 to 4 hours, and daily, access site checks, and creatinine clearance.

Management of bleeding. Stop infusion. For eptifibatide and tirofiban, platelet function returns within hours. For abciximab, platelet transfusion restores function.

Referral and escalation. Any thrombocytopenia under 50 x 10^9/L, or unexplained fall of over 50%, needs the drug stopped and haematology input.

Special groups. Kidney disease: dose reduction or avoidance. Older adults: higher bleeding risk. Pregnancy: limited data. Low body weight: weight-based dosing with capping.