Glycoprotein IIb/IIIa Inhibitors

Presentation and Cause

Glycoprotein IIb/IIIa inhibitors are a class of drugs that prevent the binding of fibrinogen to platelets. This class of drugs includes abciximab, eptifibatide, and tirofiban.¹Glycoprotein IIb/IIIa inhibitors are approved by the FDA to treat acute coronary syndromes (ACS) including unstable angina and non-ST elevation myocardial infarction that needs percutaneous coronary intervention (PCI).^1-3

Symptoms of ACS include chest pain, nausea, sweating, dizziness or lightheadedness, shortness of breath, and discomfort or pain in the jaw, neck, back, stomach, or arms.⁴ Myocardial infarction symptoms can appear quickly, whereas symptoms of unstable angina often do not follow a pattern and may actually get worse during rest.

Risk factors for ACS include diabetes, smoking, high cholesterol, hypertension, obesity or overweight, family history of heart disease, stroke, or chest pain.⁴

The American College of Cardiology/American Heart Association currently recommends use of glycoprotein IIb/IIIa inhibitors in the treatment of ACS in patients:

Unable to tolerate P2Y12 inhibitors, such as clopidogrel, ticlopidine, ticagrelor, prasugrel, and cangrelor⁵
With allergy to P2Y12 inhibitors¹
Undergoing PCI who have gotten P2Y12 inhibitors but have a high risk of thrombus and an aspirin allergy.¹

Diagnostic Workup/Differential Diagnosis

Patients presenting with chest pain should undergo a 12-lead electrocardiogram.⁶ Treatment is based on whether there is ST-segment elevation myocardial infarction (STEMI) present or not. If there is STEMI, the patient should undergo PCI or fibrinolytic therapy. If there is no STEMI, ACS risk should be classified as low, intermediate, or high. Cardiac troponin levels aid in determining risk.

Other causes of chest pain to rule out include:⁶

Acute aortic dissection
Pericarditis
Heart failure
Gallbladder disease
Gastroesophageal reflux
Nonulcer dyspepsia
Peptic ulcer
Pancreatitis
Costochondritis
Strained chest muscle
Panic attack
Somatoform disorder
Pulmonary causes, such as pneumonia, pneumothorax, or pulmonary embolism

Before a decision is made to initiate a glycoprotein IIb/IIIa inhibitor, check INR, PT, and aPTT levels, ask about any drug allergies or intolerances, and review possible contraindications of treatment with glycoprotein IIb/IIIa inhibitors.¹

Glycoprotein IIb/IIIa Inhibitors: Pharmacotherapy Management

Glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors block subunits α and β on glycoprotein receptors of the platelet’s membrane. The GPIIb/IIIa receptor is the primary platelet receptor in platelet aggregation. This inhibition interferes with fibrinogen and von Willebrand factor binding. Drugs in this class are given intravenously along with aspirin and include abciximab, tirofiban, and eptifibatide.¹

Abciximab is approved to prevent ischemic complications in patients who are undergoing percutaneous coronary intervention (PCI), or with unstable angina that does not respond to antianginal drugs when PCI is scheduled within 24 hours.⁷

The recommended dosage of abciximab in adults is a 0.25 mg/kg intravenous bolus given 10 to 60 minutes before PCI. This is followed by a continuous intravenous infusion of 0.125 µg/kg/min (to a maximum of 10 µg/min) for 12 hours.

Patients with unstable angina that is not responsive to medical therapy and who are scheduled to undergo PCI within 24 hours may receive a bolus dose of abciximab 0.25 mg/kg followed by an 18- to 24-hour intravenous infusion of 10 µg/min, stopping one hour after the PCI.

Eptifibatide is approved in patients with ACS, and those undergoing PCI and stenting to lower the risk of death or new myocardial infarction.² The dosage is as follows:

ACS: 180 mcg/kg IV bolus immediately after diagnosis followed by continuous infusion at 2 mcg/kg/min
PCI: 180 mcg/kg IV bolus immediately before PCI followed by continuous infusion at 2 mcg/kg/min Add a second 180 mcg/kg bolus at 10 minutes

Tirofiban is approved in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) to lower the rate of death, myocardial infarction, refractory ischemia, and need to repeat cardiac procedure.³ The dosage is 25 mcg/kg given intravenously within 5 minutes and then 0.15 mcg/kg/min for up to 18 hours.

Complications of Glycoprotein IIb/IIIa Inhibitors

Glycoprotein IIb/IIIa inhibitors side effects include bleeding, hypotension, bradycardia, and thrombocytopenia.¹ Other complications to monitor include the risk of anaphylaxis.⁷

Absolute contraindications to treatment with glycoprotein IIb/IIIa inhibitors include major bleeding diathesis, active internal bleeding, and history of hemorrhagic stroke within 30 days.¹ Relative contraindications include history of thrombocytopenia, stroke, severe hypertension, or major surgery in the past six weeks. Possible contraindications include renal impairment and intracranial disease.

Monitoring

Patients should be monitored for thrombocytopenia which may occur as soon as 24 hours after treatment with glycoprotein IIb/IIIa inhibitors.¹ The platelet count should be checked within four hours of the start of the infusion and again at 24 hours. Signs and symptoms of bleeding, such as blood in the urine or vomit, should also be monitored.⁷

The infusion of glycoprotein IIb/IIIa inhibitors should be stopped if the platelet count drops below 100,000/mm.¹ Patients at high risk for thrombus should remain in intensive care if the glycoprotein IIb/IIIa inhibitors need to be continued. Typically, it takes up to two weeks for the platelet count to return to normal.

Because eptifibatide is cleared by the kidneys, patients with decreased renal function (ie, estimated creatinine clearance less than 50 ml/min) should receive the following adjusted dosage of eptifibatide: 180 mcg/kg IV bolus just before PCI followed by continuous infusion of 1 mcg/kg/min and a second bolus of 180 mcg/kg.²

References

1. Tummala R, Rai MP. Glycoprotein IIb/IIIa Inhibitors. In: StatPearls. NCBI Bookshelf version. StatPearls Publishing; 2022.

2. U.S. Food and Drug Administration. Integrilin (eptifibatide) injection, for intravenous use. February 2021. Accessed September 8, 2022.

3. U.S. Food and Drug Administration. Aggrastat (tirofiban hydrochloride) injection, for intravenous use. May 2019. Accessed September 8, 2022.

4. Acute Coronary Syndrome. American Heart Association. 2022. Accessed September 8, 2022.

5. U.S. National Library of Medicine. Antiplatelet drugs – P2Y12 inhibitors. July 2020. Accessed September 8, 2022.

6. Barstow C, Rice M, McDivitt JD. Acute Coronary Syndrome: Diagnostic Evaluation. Am Fam Physician. 2017;95(3):170-177.

7. U.S. Food and Drug Administration. ReoPro® abciximab for intravenous administration. August 2019. Accessed September 8, 2022.

Author Bio

Jen Seabright, PharmD, is a freelance medical writer located in Pittsburgh, PA.