What is the recommended dose of Tissue Plasminogen Activator (TPA) for the treatment of ST-Elevation Myocardial Infarction (STEMI)?

TPA Dosing for STEMI

For STEMI treatment, Alteplase (tPA) should be administered as a 15 mg IV bolus, followed by 0.75 mg/kg over 30 minutes (not to exceed 50 mg), then 0.5 mg/kg over 60 minutes (not to exceed 35 mg), with a total dose not exceeding 100 mg. 1

Fibrinolytic Agent Options for STEMI

When primary PCI is not immediately available, fibrinolytic therapy becomes a critical reperfusion strategy. The following fibrinolytic agents are recommended with their specific dosing regimens:

1. Alteplase (tPA):

   • 15 mg IV bolus
   • 0.75 mg/kg over 30 minutes (maximum 50 mg)
   • 0.5 mg/kg over 60 minutes (maximum 35 mg)
   • Total dose not to exceed 100 mg 1

2. Tenecteplase (TNK-tPA) - Weight-based single IV bolus:

   • <60 kg: 30 mg
   • 60-69 kg: 35 mg
   • 70-79 kg: 40 mg
   • 80-89 kg: 45 mg
   • ≥90 kg: 50 mg 1

3. Reteplase (rPA):

   • 10 U + 10 U IV bolus given 30 minutes apart 1

4. Streptokinase (no longer marketed in the US):

   • 1.5 million units over 30-60 minutes IV 1

Adjunctive Therapy with Fibrinolytic Treatment

Fibrinolytic therapy should always be accompanied by appropriate antithrombotic therapy:

Antiplatelet Therapy

• Aspirin: 162-325 mg loading dose (oral or IV if oral ingestion not possible), followed by 81-325 mg daily maintenance 1
• Clopidogrel: 300 mg loading dose for patients <75 years of age, 75 mg for patients >75 years of age, followed by 75 mg daily for at least 14 days 1

Anticoagulant Therapy

Anticoagulation should be administered for a minimum of 48 hours, and preferably for the duration of the index hospitalization (up to 8 days) or until revascularization if performed 1.

Important Considerations

Contraindications to Fibrinolytic Therapy

Absolute contraindications include:

• Prior intracranial hemorrhage
• Known cerebral vascular lesion
• Malignant intracranial neoplasm
• Ischemic stroke within 3 months (except acute ischemic stroke within 4.5 hours)
• Suspected aortic dissection
• Active bleeding or bleeding diathesis
• Significant facial or head trauma within 3 months
• Intracranial/intraspinal surgery within 2 months
• Severe uncontrolled hypertension 1

Timing of Administration

• Fibrinolytic therapy should be administered within 12 hours of symptom onset, with greatest benefit when given within the first 3 hours 1
• Door-to-needle time should be minimized (target <30 minutes) 2

Efficacy Considerations

• Patency rates (90-minute TIMI 2 or 3 flow) vary by agent:
  • Tenecteplase: 85%
  • Reteplase: 84%
  • Alteplase: 73-84%
  • Streptokinase: 60-68% 1

Clinical Decision Making

When choosing between fibrinolytic agents, consider:

1. If immediate PCI is not available within 90 minutes of first medical contact
2. Patient presents within 12 hours of symptom onset
3. No contraindications to fibrinolytic therapy
4. For most patients, newer fibrin-specific agents (tPA, TNK-tPA, rPA) are preferred over streptokinase due to higher patency rates 1

Remember that primary PCI remains the preferred reperfusion strategy when available in a timely manner, but fibrinolytic therapy is a critical alternative when PCI is not readily accessible.