The European Society of Cardiology (ESC) guideline for myocardial revascularisation recommends the use of glycoprotein IIb/IIIa-inhibitors in bail-out situations (i.e., intra-procedure thrombus formation, slow flow, threatened vessel closure) during elective PCI, and in NSTE-ACS patients with evidence of high intracoronary thrombus burden. Currently, the ESC guideline discourages the upstream use of glycoprotein IIb/IIIa-inhibitors (Neumann, F-J et al).

In 2010, NICE recommended that a glycoprotein IIb/IIIa inhibitor (e.g., abciximab, eptfibatide or tirofiban) is considered as an adjunct to percutaneous coronary intervention (PCI) for all patients with diabetes undergoing elective PCI, and for those patients undergoing complex procedures (for example, multi-vessel PCI, insertion of multiple stents, vein graft PCI or PCI for bifurcation lesions).

Eptifibatide is a glycoprotein (GP) IIb/IIIa inhibitor. It inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor and other adhesive ligands to the glycoprotein (GP) IIb/IIIa receptors. The efficacy is dose- and concentration- dependent.

ESPRIT study explored the benefit of eptifibatide in 2,064 patients undergoing non-urgent PCI with coronary stent implantation. Eptifibatide therapy was shown to significantly reduce the primary endpoint (composite of death, MI, urgent target vessel revascularisation (UTVR) and thrombotic bailout within 48 hours of randomisation). The incidence of the combined endpoint death or myocardial infarction after 48 hours was also significantly lower in the eptifibatide group compared with placebo (O’Shea et al. 2002).

In UK, eptifibatide is licensed for prevention of early myocardial infarction in patients with unstable angina or NSTEMI with the last episode of chest pain occurring within 24 hours and with ECG changes and/or elevated cardiac enzymes.

This guideline specifically looks at the unlicensed use of eptifibatide in bail-out situations or in patients with high thrombus burden during PCI.

• 2mg/ml in 10mls vial solution for injection (for bolus dose)

• 75mg/100mls vial solution for infusion (for continuous infusion)

As mentioned, use of eptifibatide in this setting is not currently licensed and the dosage schedule below is that used in the ESPRIT study.

For patients with creatinine clearance > 50mls/min:

Eptifibatide should be administered as a 180 micrograms/kg IV bolus

followed by a 2.0 micrograms/kg/minute infusion for up to 18-24 hours

with a second 180 micrograms/kg IV bolus given 10 minutes after the initial bolus.

(See table below for dose recommendation for patients with renal function > 50mls/min.)

Please note that the above is based on the ESPRIT study but, in practice, some patients would not require prolong infusion of eptifibatide (i.e., stop after 6 hours of infusion). Duration of treatment should be reviewed / guided by the cardiology consultant.

A bolus dose of unfractionated heparin (UFH) should be given at the standard PCI dose according to the operator’s usual practice.

The following table is provided as a guide to dosage adjustment by weight in patient with creatinine clearance > 50mls/min: (BSUHT 2009)

Eptifibatide should be given with aspirin, clopidogrel (or ticagrelor or prasugrel) and dalteparin or fondaparinux as per the trust’s ACS guideline.

Renal excretion accounted for approximately 50 % of total body clearance of eptifibatide; while approximately 50 % of the amount cleared is excreted unchanged. The dose does not require adjustment in mild-moderate renal impairment.

For patients with MODERATE renal impairment
(creatinine clearance >30mls/min but < 50mls/min),
give the usual bolus doses(s) followed by an infusion at 1.0 microgram/kg/minute.

Use of eptifibatide in SEVERE renal impairment (creatinine clearance <30ml/minute) is contraindicated.

Eptifibatide must not be used to treat patients with:

• hypersensitivity to the active substance or to any of the excipients

• evidence of gastrointestinal bleeding, gross genitourinary bleeding or other active abnormal bleeding within the previous 30 days

• history of stroke within 30 days or any history of haemorrhagic stroke

• known history of intracranial disease (neoplasm, arteriovenous malformation, aneurysm)

• major surgery or severe trauma within past 6 weeks

• thrombocytopenia (platelet counts < 100,000 cells/mm3)

• prothrombin time > 1.2 times control, or International Normalized Ratio (INR) ≥ 2.0

• severe hypertension (systolic blood pressure > 200 mm Hg or diastolic blood pressure > 110 mm Hg on antihypertensive therapy)

• severe renal impairment (creatinine clearance < 30 ml/min) or dependency on renal dialysis

• clinically significant hepatic impairment

• concomitant or planned administration of another parenteral glycoprotein (GP) IIb/IIIa inhibitor

• pregnancy (unless benefits outweigh risks)

• breast feeding

During treatment, close monitoring of the patients’ clinical status (monitor closely for any signs of bleeding) and haematological parameters are required. The manufacturers recommend the following schedule: (BSUHT 2009)

The majority of adverse reactions experienced by patients treated with eptifibatide were generally related to bleeding or to cardiovascular events that occur frequently in this patient population.

Cases of adverse bleeding events can usually be managed by discontinuation of the drug and where applicable application of pressure.

NICE (2010) Guidance on the use of glycoprotein IIb/IIIa inhibitors in the treatment of acute coronary syndromes. TA47. Available at: https://www.nice.org.uk/guidance/ta47.

O’Shea, J.C. et al. (2002) ‘Long-term efficacy of platelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention’, JAMA, 287(5), pp. 618-621. Available at: https://jamanetwork.com/journals/jama/fullarticle/194603.

Neumann, F-J. et al. (2018) ‘2018 ESC/EACTS guidelines on myocardial revascularisation’, European Heart Journal, 40(2), pp. 87-165. Available at: https://academic.oup.com/eurheartj/article/40/2/87/5079120. 

This guideline has been registered with the Trust. However, clinical guidelines are guidelines only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt, contact a senior colleague or expert. Caution is advised when using guidelines after the review date.

This guideline is for use in Frimley Health NHS Foundation Trust hospitals only. Any use outside this location will not be supported by the Trust and will be at the risk of the individual using it.

Version History

Related Documents