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.

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.

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.

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.

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.
• STEMI Managed by PCI:
  • With GP IIb/IIIa receptor antagonist planned: 50-70 units/kg IV bolus to achieve therapeutic ACT.
  • Without GP IIb/IIIa receptor antagonist planned: 70-100 units/kg bolus to achieve therapeutic ACT.
  • Guideline Recommendation: 1C recommendation from 2013 AHA STEMI Guidelines when managed with PCI.
• STEMI Managed with Fibrinolytics:
  • Weight-based IV bolus and infusion adjusted to obtain aPTT of 1.5 to 2.0 times control for 48 hours or until revascularization.
  • IV bolus of 60 units/kg (maximum 4000 units) followed by an infusion of 12 units/kg/hour (maximum 1000 units/hour), adjusted to maintain aPTT at 1.5 to 2.0 times control (approximately 50 to 70 seconds) for 48 hours or until revascularization.
  • Guideline Recommendation: COR 1, LOE C.

Clinical Considerations:

• Adjust dose based on aPTT to maintain therapeutic levels.
• Monitor for signs of bleeding and heparin-induced thrombocytopenia (HIT).

Clinical Pearls:

• Rapid Reversal: UFH has a short half-life and can be rapidly reversed with protamine sulfate if needed.
• Monitoring: Requires frequent aPTT monitoring to ensure therapeutic levels.

References: 2013 ACCF/AHA STEMI Guidelines.

2. Enoxaparin (Low Molecular Weight Heparin)

Dosing:

• STEMI Managed by PCI:
  • Not typically used in combination with PCI due to preference for UFH or bivalirudin.
• STEMI Managed with Fibrinolytics:
  • Age <75 years: 30 mg IV bolus followed in 15 minutes by 1 mg/kg subcutaneously every 12 hours (maximum 100 mg for the first 2 doses).
  • Age ≥75 years: No bolus; 0.75 mg/kg subcutaneously every 12 hours (maximum 75 mg for the first 2 doses).
  • Regardless of age, if CrCl <30 mL/min: 1 mg/kg subcutaneously every 24 hours.
  • Duration: For the index hospitalization, up to 8 days or until revascularization.
  • Guideline Recommendation: COR 1, LOE A.
• NSTEMI Managed by PCI:
  • 1 mg/kg subcutaneously every 12 hours (maximum 100 mg for the first 2 doses).
  • 30 mg IV bolus if beyond 8 hours since last dose.

Clinical Considerations:

• Avoid in patients with severe renal impairment (CrCl <15 mL/min).
• Monitor for signs of bleeding.

Clinical Pearls:

• Predictable Pharmacokinetics: Enoxaparin has more predictable anticoagulant effects compared to UFH.
• Longer Half-Life: Longer duration of action allows for less frequent dosing.

References: 2014 ACC/AHA NSTEMI Guidelines.

3. Bivalirudin

Dosing:

• Initial bolus: 0.75 mg/kg IV.
• Continuous infusion: 1.75 mg/kg/hour during PCI.
• An additional bolus of 0.3 mg/kg can be given if needed.
• Reduce infusion to 1 mg/kg/hour with estimated CrCl <30 mL/min.

Clinical Considerations:

• Typically reserved for patients undergoing PCI, particularly those with a high risk of bleeding.
• Preferred over UFH with GP IIb/IIIa receptor antagonist in patients at high risk of bleeding.

Clinical Pearls:

• Lower Bleeding Risk: Associated with a lower risk of bleeding compared to UFH with GP IIb/IIIa inhibitors.
• No HIT: Does not cause heparin-induced thrombocytopenia (HIT).

Guideline Recommendations:

ACC/AHA Guidelines: Recommended for patients undergoing PCI (Class I, Level of Evidence B).

References: 2013 ACCF/AHA STEMI Guidelines.

4. Fondaparinux

Dosing:

• STEMI Managed with Fibrinolytics:
  • Initial dose 2.5 mg IV, then 2.5 mg subcutaneously daily starting the following day, for the index hospitalization up to 8 days or until revascularization.
  • Guideline Recommendation: COR 1, LOE B.
• STEMI Managed by PCI:
  • Not recommended as the sole anticoagulant for primary PCI.

Clinical Considerations:

• Contraindicated in patients with severe renal impairment (CrCl <30 mL/min).
• Monitor for signs of bleeding.

Clinical Pearls:

• No HIT: Fondaparinux does not cause heparin-induced thrombocytopenia (HIT).
• Adjunct Therapy: When used in PCI, it must be combined with UFH or bivalirudin due to the risk of catheter thrombosis.

References: 2013 ACCF/AHA STEMI Guidelines.