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Pharmacy & Acute Care University
Pharmacy & Acute Care University
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Acute Care Cardiology

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  1. Acute Coronary Syndrome
    8 Topics
  2. ADHF
  3. Lesson
  4. Hypertensive Crisis
  5. Atrial Arrythmias
  6. Ventricular Arrythmias
  7. Bradycardia
  8. Lesson
  9. Aortic Dissection

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Acute Care Cardiology Acute Coronary Syndrome Pharmacologic Intervention 2: Acute Coronary Syndrome
Lesson 1, Topic 4
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Pharmacologic Intervention 2: Acute Coronary Syndrome

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IV GP IIb/IIIa Receptor Antagonists and Anticoagulants

ACS Medications: IV GP IIb/IIIa Receptor Antagonists and Anticoagulants

IV GP IIb/IIIa Receptor Antagonists

IV GP IIb/IIIa receptor antagonists are used in conjunction with unfractionated heparin (UFH) or bivalirudin to prevent platelet aggregation and thrombus formation in patients with ACS, particularly during percutaneous coronary intervention (PCI).

1. Abciximab

Dosing:

  • Initial bolus: 0.25 mg/kg IV.
  • Continuous infusion: 0.125 mcg/kg/min (maximum 10 mcg/min) for 12 hours.

Clinical Considerations:

  • Abciximab is a monoclonal antibody that binds to the GP IIb/IIIa receptor on platelets, inhibiting aggregation.
  • It is primarily used in patients undergoing PCI, especially those with high-risk features.
  • Monitor for thrombocytopenia and bleeding.

Clinical Pearls:

  • Duration of Action: Abciximab has a longer half-life compared to other GP IIb/IIIa inhibitors, which can be advantageous in maintaining platelet inhibition during and after PCI.
  • Bleeding Risk: Due to its potent antiplatelet effects, careful monitoring for bleeding is essential.
  • Reversibility: Platelet function can be restored by transfusing platelets if significant bleeding occurs.

Guideline Recommendations:

ACC/AHA Guidelines: “Abciximab can be used as an adjunct to UFH in patients undergoing PCI (Class IIa, Level of Evidence A).”

Evidence from Studies:

EPIC Trial (1994): Demonstrated that abciximab significantly reduces the risk of ischemic complications during high-risk PCI.

Reference: The EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Engl J Med. 1994;330(14):956-961.

2. Tirofiban

Dosing:

  • Initial bolus: 25 mcg/kg IV over 3 minutes.
  • Continuous infusion: 0.15 mcg/kg/min for up to 18 hours.
  • In patients with CrCl <30 mL/min: Reduce infusion rate by 50%.

Clinical Considerations:

  • Tirofiban is a non-peptide tyrosine derivative that reversibly inhibits the GP IIb/IIIa receptor.
  • It is often used in patients undergoing PCI or those with unstable angina/NSTEMI.
  • Monitor renal function and adjust the dose in renal impairment.
  • However, its use has declined due to elevated bleeding risk, and it is often reserved for bail-out situations in many centers. Additionally, tirofiban is not available in the United States.

Clinical Pearls:

  • Rapid Onset: Provides quick platelet inhibition, making it suitable for acute settings.
  • Reversibility: The effects of tirofiban are quickly reversible upon discontinuation, which can be beneficial in managing bleeding complications.
  • Adjustments for Renal Impairment: Dose adjustments are necessary in patients with renal dysfunction to prevent excessive bleeding.

Guideline Recommendations:

ACC/AHA Guidelines: “Tirofiban can be used as an adjunct to UFH in patients with NSTEMI or those undergoing PCI (Class IIa, Level of Evidence B).”

Evidence from Studies:

PRISM-PLUS Trial (1998): Showed that tirofiban reduces the risk of death, MI, or refractory ischemia in patients with UA/NSTEMI.

Reference: The PRISM-PLUS Investigators. Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non–Q-wave myocardial infarction. N Engl J Med. 1998;338(21):1488-1497.

3. Eptifibatide

Dosing:

  • Initial bolus: 180 mcg/kg IV.
  • Continuous infusion: 2 mcg/kg/min for up to 18-24 hours.
  • A second bolus of 180 mcg/kg IV is administered 10 minutes after the first bolus.
  • In patients with CrCl <50 mL/min: Reduce infusion rate by 50%.

Clinical Considerations:

  • Eptifibatide is a cyclic heptapeptide that reversibly inhibits the GP IIb/IIIa receptor.
  • It is used in patients with ACS undergoing PCI or those with UA/NSTEMI.
  • Monitor renal function and adjust the dose in renal impairment.

Clinical Pearls:

  • Double Bolus: The initial and second bolus doses ensure adequate platelet inhibition during the critical early phase of PCI.
  • Reversibility: Eptifibatide’s effects are reversible, which can help manage bleeding complications.
  • Adjustments for Renal Impairment: Dose adjustments are necessary in patients with renal dysfunction to prevent excessive bleeding.

Guideline Recommendations:

ACC/AHA Guidelines: “Eptifibatide is recommended for patients with UA/NSTEMI undergoing an early invasive strategy (Class I, Level of Evidence A).”

Evidence from Studies:

PURSUIT Trial (1998): Demonstrated that eptifibatide reduces the incidence of death and nonfatal MI in patients with ACS.

Reference: The PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. N Engl J Med. 1998;339(7):436-443.

Clinical Pearls for All IV GP IIb/IIIa Receptor Antagonists:

  • Adjunct Therapy: These agents are used in conjunction with UFH or bivalirudin to provide additional platelet inhibition during PCI.
  • Monitoring: Close monitoring of platelet counts and renal function is necessary to adjust doses and prevent complications.
  • Bleeding Risk: Patients receiving these agents are at increased risk of bleeding; therefore, careful assessment and management of bleeding risks are essential.
  • Reversibility: The effects of GP IIb/IIIa inhibitors are reversible, and platelet transfusion can be used to manage severe bleeding complications.

Specific Data for STEMI and NSTEMI/UA:

  1. STEMI:
    • Abciximab: Recommended in patients undergoing primary PCI for STEMI, particularly those with high thrombotic risk (e.g., large thrombus burden, inadequate P2Y12 inhibition).
    • Tirofiban and Eptifibatide: Can be used in STEMI patients undergoing PCI, although their use is less common compared to abciximab. They may be considered in patients who are not adequately pre-treated with P2Y12 inhibitors or in bail-out situations.
  2. NSTEMI/UA:
    • All Agents (Abciximab, Tirofiban, Eptifibatide):
      • Recommended for use in patients undergoing an early invasive strategy or those with high-risk features (e.g., positive troponins, dynamic ST changes).
      • These agents help reduce the risk of ischemic complications and improve outcomes when used as adjuncts to anticoagulants (UFH or bivalirudin) during PCI.

Anticoagulants

Anticoagulants are used alongside antiplatelet agents to prevent the propagation of clots in ACS. The selection of anticoagulants depends on the type of ACS and the therapeutic strategy (PCI or fibrinolysis).

1. Unfractionated Heparin (UFH)

Dosing:

  • General Use:
    • Initial bolus: 60 units/kg (maximum 4000 units).
    • Continuous infusion: 12 units/kg/hour (maximum 1000 units/hour), adjusted based on aPTT.