What are the thrombolytic agents (drugs that dissolve blood clots) used for thrombolysis in myocardial infarction (MI), specifically in a patient with acute ST-elevation myocardial infarction (STEMI)?

Thrombolytic Agents for Myocardial Infarction

The recommended thrombolytic drugs for STEMI are the fibrin-specific agents: tenecteplase, alteplase, or reteplase, with tenecteplase or alteplase preferred over streptokinase for patients presenting within 6 hours of symptom onset. 1

Primary Thrombolytic Agents

The European Society of Cardiology provides Class I, Level B recommendations for the following fibrin-specific agents 1:

• Tenecteplase - administered as a single IV bolus (weight-tiered dosing: 30-50 mg based on body weight), with half-dose recommended for patients ≥75 years of age 1, 2, 3
• Alteplase (tPA) - administered as accelerated infusion over 90 minutes: 15 mg IV bolus, then 0.75 mg/kg over 30 minutes (max 50 mg), then 0.50 mg/kg over 60 minutes (max 35 mg) 1, 3, 4
• Reteplase - administered as double bolus injection 1, 5, 4

For patients presenting within 6 hours of symptom onset, alteplase or tenecteplase are superior to streptokinase and should be used preferentially. 5, 4

Non-Fibrin-Specific Agents (Less Preferred)

• Streptokinase - may be used when fibrin-specific agents are unavailable or contraindicated (e.g., known allergy to streptokinase mandates use of alteplase, reteplase, or tenecteplase instead) 5, 4
• Anistreplase - rarely used currently 5, 4

Mandatory Adjunctive Antiplatelet Therapy

All patients receiving thrombolytics must receive dual antiplatelet therapy 1:

• Aspirin 160-325 mg orally or IV immediately, then 75-162 mg daily indefinitely (Class I, Level B) 1, 5, 4
• Clopidogrel 300 mg loading dose (for patients <75 years), then 75 mg daily for at least 14 days up to 12 months (Class I, Level A) 1, 2, 4

Mandatory Anticoagulation Co-Therapy

Anticoagulation is required until revascularization or for hospital duration up to 8 days (Class I, Level A) 1, 2:

Preferred anticoagulation regimen:

• Enoxaparin IV bolus followed by subcutaneous dosing (preferred over unfractionated heparin) 1, 2, 4

Alternative anticoagulation options:

• Unfractionated heparin (UFH) - weight-adjusted IV bolus (60 units/kg, max 4000 units) followed by infusion (12 units/kg/hr, max 1000 units/hr) targeting aPTT 50-75 seconds 1, 2, 5, 4
• Fondaparinux - IV bolus followed by subcutaneous dose 24 hours later, specifically for patients receiving streptokinase (Class IIa, Level B) 1, 2

Critical Timing Considerations

Thrombolytic therapy must be initiated within 10 minutes of STEMI diagnosis, preferably in the pre-hospital setting (Class I, Level A). 1, 2 The greatest mortality benefit occurs when treatment is administered within 6 hours of symptom onset, with efficacy decreasing substantially after 3 hours. 2, 6 Treatment is indicated up to 12 hours from symptom onset in patients with persistent ST-segment elevation. 1, 5, 4

Important Clinical Pitfalls

Avoid fondaparinux as sole anticoagulation during PCI - it increases catheter thrombosis risk and requires additional UFH or bivalirudin. 2

Dose adjustment required for elderly patients - consider half-dose tenecteplase for patients ≥75 years to reduce bleeding risk while maintaining efficacy. 1, 2

All patients must be transferred to a PCI-capable center immediately after fibrinolysis (Class I, Level A), with rescue PCI indicated if fibrinolysis fails (defined as <50% ST-segment resolution at 60-90 minutes) or if hemodynamic/electrical instability develops. 1