What is the indication for Agrastat (tirofiban)?

Indication for Agrastat (Tirofiban)

Agrastat (tirofiban) is indicated to reduce the rate of thrombotic cardiovascular events (death, myocardial infarction, or refractory ischemia/repeat cardiac procedure) in patients with non-ST elevation acute coronary syndrome (NSTE-ACS). 1

Primary Indication

• NSTE-ACS patients including unstable angina and non-Q-wave myocardial infarction who present with chest pain at rest within 24 hours and either ECG changes indicating ischemia or elevated cardiac biomarkers 2

Specific Clinical Scenarios Where Tirofiban Provides Benefit

High-Risk NSTE-ACS Patients Undergoing PCI

• Patients with ongoing ischemia and/or dynamic ECG changes who require percutaneous coronary intervention derive the greatest benefit 2, 3
• The drug should be administered in combination with aspirin and heparin (either unfractionated or low-molecular-weight heparin) 2
• Particularly beneficial when used as a bailout strategy for thrombotic complications during or after PCI 4

Evidence-Based Patient Selection

Patients most likely to benefit include those with:

• Ischemic ECG changes (ST-segment depression or T-wave changes) within 12 hours before enrollment 2
• Elevated cardiac enzymes (CK-MB or troponin) 2
• Refractory ischemia despite medical therapy 2
• High-risk features warranting early invasive strategy 2

Administration Strategy

Timing Relative to PCI

• Can be administered "upstream" (before angiography) for 48-108 hours in high-risk patients, with 30-35% undergoing PCI while on study drug 2
• Alternatively, can be given at the time of PCI as bailout therapy for thrombotic complications 4, 2
• The benefit is magnified during the intervention phase compared to medical management alone 2

Dosing Regimen

• Loading dose: 25 mcg/kg IV over 5 minutes 5, 1
• Maintenance infusion: 0.15 mcg/kg/min for up to 18 hours 5, 1
• Renal adjustment required: For creatinine clearance ≤60 mL/min, reduce maintenance dose to 0.075 mcg/kg/min (50% reduction) 5, 1

Important Clinical Context

Combination Therapy Requirements

• Must be used with heparin - tirofiban alone (without heparin) was associated with increased mortality and was discontinued in the PRISM-PLUS trial 2
• Should be combined with aspirin as standard background therapy 2
• Can be safely combined with clopidogrel 600 mg loading dose in contemporary practice 4

Contraindications and Cautions

• Contraindicated in patients with:
  • Known hypersensitivity to tirofiban 1
  • History of thrombocytopenia with prior tirofiban exposure 1
  • Active internal bleeding or bleeding diathesis 1
  • Major surgery or severe trauma within the previous month 1

Clinical Outcomes Data

• 7-day composite endpoint reduction: 32% relative risk reduction (from 17.9% to 12.9%) in death, MI, or refractory ischemia when combined with heparin in PRISM-PLUS 2
• 30-day benefit: 22-30% relative risk reduction in death or MI maintained at 30 days 2
• Early intervention benefit: 38% relative reduction in composite endpoint at 48 hours in RESTORE trial 2, 6

Common Pitfalls to Avoid

• Never use tirofiban as monotherapy without heparin in NSTE-ACS patients - this increases mortality risk 2
• Do not use in STEMI patients treated with thrombolysis - there is no indication for this combination 3
• Monitor platelet counts regularly - thrombocytopenia occurs in approximately 0.5-1.1% of patients and requires immediate discontinuation 2, 7, 8
• Adjust dose for renal impairment - failure to reduce the maintenance infusion rate in patients with CrCl ≤60 mL/min increases bleeding risk due to prolonged half-life 7, 5