Recommended Dosing of Alteplase for Fibrinolysis in Acute Myocardial Infarction
For patients with acute myocardial infarction requiring fibrinolysis, Alteplase should be administered as a 15 mg intravenous bolus, followed by 0.75 mg/kg over 30 minutes (up to 50 mg), then 0.5 mg/kg over 60 minutes (up to 35 mg), with a total dose not exceeding 100 mg. 1
Dosing Regimen Details
- Initial dose: 15 mg IV bolus 1
- Second phase: 0.75 mg/kg over 30 minutes (maximum 50 mg) 1
- Third phase: 0.5 mg/kg over 60 minutes (maximum 35 mg) 1
- Total maximum dose: 100 mg 1
- Required adjunctive therapy: Intravenous heparin for 24 to 48 hours 1
Adjunctive Antithrombotic Therapy
Antiplatelet Therapy
- Aspirin: Starting dose of 150-500 mg orally or 250 mg IV if oral ingestion is not possible 1
- Clopidogrel: Loading dose of 300 mg orally if aged ≤75 years, followed by maintenance dose of 75 mg/day 1
Anticoagulation
- Unfractionated heparin: 60 U/kg IV bolus (maximum 4000 U) followed by IV infusion of 12 U/kg/hour (maximum 1000 U/hour) for 24-48 hours 1
- Enoxaparin (preferred over UFH): 1
- For patients <75 years: 30 mg IV bolus followed 15 minutes later by 1 mg/kg SC every 12 hours
- For patients >75 years: No IV bolus; start with first SC dose of 0.75 mg/kg (maximum 75 mg for first two doses)
- For patients with creatinine clearance <30 mL/min: SC doses given once every 24 hours
Clinical Considerations
- Alteplase is a fibrin-specific agent and is recommended over non-fibrin specific agents like streptokinase 1
- Fibrinolysis should be initiated within 12 hours of symptom onset 1
- Fibrinolysis is recommended when primary PCI cannot be performed by an experienced team within 120 minutes of first medical contact 1
- In patients presenting early (<2 hours after symptom onset) with a large infarct and low bleeding risk, fibrinolysis should be considered if time from first medical contact to balloon inflation is >90 minutes 1
Post-Fibrinolysis Management
- Transfer to a PCI-capable center following fibrinolysis is indicated in all patients 1
- Rescue PCI is indicated immediately if fibrinolysis fails (<50% ST-segment resolution at 60 minutes) 1
- Emergency PCI is indicated for recurrent ischemia or evidence of reocclusion after initially successful fibrinolysis 1
- Optimal timing of angiography for stable patients after successful lysis: 3-24 hours 1
Common Pitfalls and Caveats
- Do not exceed the maximum total dose of 100 mg 1
- Alteplase requires adjunctive IV heparin therapy for 24-48 hours 1
- Unlike streptokinase, Alteplase does not result in antibody formation and can be re-administered if needed 1
- Careful monitoring of aPTT is essential when using heparin; values >70 seconds are associated with increased risk of bleeding, reinfarction, and death 1
- The risk of hemorrhagic stroke is higher with Alteplase than with streptokinase 2
- Tenecteplase, aspirin, enoxaparin, and clopidogrel comprise the most extensively studied antithrombotic combination for a pharmacoinvasive strategy 1