What is the preferred thrombolytic agent, alteplase (tissue plasminogen activator, tPA) or streptokinase, for which indications?

Alteplase vs Streptokinase: Preferred Agent by Indication

For acute myocardial infarction, alteplase (using the accelerated 90-minute regimen) is the preferred thrombolytic agent over streptokinase due to superior mortality reduction, though at significantly higher cost and with increased risk of intracranial hemorrhage. 1

Acute Myocardial Infarction (AMI)

Efficacy Comparison

Alteplase demonstrates superior outcomes in AMI:

• Accelerated alteplase (≤100mg over 90 minutes) achieves 75% 90-minute patency rates and 54% TIMI grade 3 flow, compared to streptokinase's 50% patency and 32% TIMI grade 3 flow 1
• Mortality rates favor alteplase at 7.2% versus streptokinase at 7.3-10.5% in comparative trials 1
• The GUSTO trial demonstrated significant 30-day survival advantage for accelerated alteplase over streptokinase, maintained for at least 1 year 2
• When combined with aspirin within 4 hours, streptokinase achieved 53% odds reduction in mortality (6.4% vs 13.1% control), though this landmark ISIS-2 trial predates modern alteplase regimens 1

Safety Profile Differences

Critical bleeding risk considerations:

• Alteplase carries higher risk of intracranial hemorrhage, particularly hemorrhagic stroke, compared to streptokinase 2, 3
• Streptokinase causes marked systemic fibrinogen depletion versus mild depletion with alteplase 1
• Streptokinase is antigenic and causes allergic reactions (hypotension most common); alteplase is non-antigenic 1
• Streptokinase cannot be re-administered as antibodies persist for at least 10 years; alteplase can be safely re-administered 1

Administration Considerations

Practical differences:

• Alteplase requires 90-minute accelerated infusion with concurrent IV heparin for 24-48 hours 1
• Streptokinase: 1.5 million units over 30-60 minutes, no mandatory heparin (though may be used 24-48 hours) 1
• Cost differential is substantial: streptokinase $294 per dose versus alteplase $2,196 per dose 1
• Pharmacoeconomic analysis estimates accelerated alteplase costs additional $32,678 per year of life saved compared to streptokinase 2

Patient Selection Algorithm for AMI

Use alteplase preferentially when:

• Anterior wall infarction (greater absolute benefit) 2
• High-risk patients including selected elderly ≤75 years 2
• Late presentation (up to 12 hours from symptom onset) 2
• Previous streptokinase exposure within 10 years 1

Consider streptokinase when:

• Cost constraints are paramount 1
• Low-risk inferior MI where stroke risk may outweigh mortality benefit 4
• Resource-limited settings 1

Acute Ischemic Stroke

Alteplase is the only FDA-approved thrombolytic for acute ischemic stroke 4

• Dose: 0.9 mg/kg (maximum 90mg) IV over 60 minutes with 10% as initial bolus over 1 minute 4
• Streptokinase is contraindicated due to lack of efficacy data and safety concerns 4

Acute Massive Pulmonary Embolism

Alteplase is preferred over streptokinase for PE:

• Alteplase reduces mortality, PE recurrence, and pulmonary artery systolic pressure compared to anticoagulation alone 5
• Dose: 100mg IV over 2 hours 4
• Network meta-analysis showed alteplase, reteplase, streptokinase, and urokinase all reduced mortality versus heparin alone, but alteplase uniquely reduced PE recurrence rate (RR=0.23,95% CI 0.04-0.65) 5
• Streptokinase showed efficacy but without the additional recurrence reduction benefit of alteplase 5

Catheter-Related Thrombosis

Alteplase (tPA) is the recommended first-line agent over streptokinase for occluded catheters:

• American College of Chest Physicians designates tPA as agent of choice in pediatric patients due to superior in vitro clot lysis, fibrin specificity, and low immunogenicity 1
• Alteplase achieves 82.9% cumulative patency after maximum two doses in pediatric studies with no intracranial hemorrhage 1
• For catheter-related venous thrombosis requiring systemic thrombolysis, tPA achieves 69% complete resolution versus 53% for streptokinase 1
• Streptokinase has lower efficacy and carries immunogenicity concerns 1

Critical Contraindications

Absolute contraindications to both agents:

• Active internal bleeding, recent intracranial/intraspinal surgery, intracranial conditions increasing bleeding risk, bleeding diathesis, severe uncontrolled hypertension 1, 4

Streptokinase-specific contraindication:

• Prior streptokinase or anistreplase administration (antibody formation) 1

Common Pitfalls to Avoid

• Do not use double-bolus alteplase regimen for AMI - trials stopped prematurely due to increased hemorrhagic stroke (1.12% vs 0.81% with accelerated infusion) 1
• Do not re-administer streptokinase - antibodies persist ≥10 years and impair activity 1
• Do not combine reduced-dose fibrinolytics with GP IIb/IIIa inhibitors routinely - increases non-cerebral bleeding without mortality benefit 1
• For AMI, ensure aspirin 150-325mg is chewed (not enteric-coated) as first dose 1