What is the preferred choice between TPA (tissue plasminogen activator) and streptokinase for thrombolysis in a patient with acute myocardial infarction (MI)?

TPA vs Streptokinase in Acute Myocardial Infarction

Accelerated tissue plasminogen activator (tPA) is the preferred thrombolytic agent for acute myocardial infarction with ST-segment elevation, as it reduces mortality by 10 additional deaths per 1000 patients treated compared to streptokinase, despite a small increase in stroke risk. 1

Mortality Benefit: The Primary Outcome

The landmark GUSTO trial demonstrated that accelerated tPA (given over 90 minutes with IV heparin) results in 10 fewer deaths per 1000 patients treated compared to streptokinase with subcutaneous heparin 1. This mortality advantage represents the most clinically significant difference between these agents and should drive treatment selection in most patients.

Earlier trials (GISSI-2/International Trials and ISIS-3) found no mortality difference between standard 3-hour tPA infusions and streptokinase, but the accelerated 90-minute tPA regimen fundamentally changed this comparison 1.

Stroke Risk: The Trade-Off

The mortality benefit of tPA comes at the cost of 3 additional strokes per 1000 patients treated compared to streptokinase 1. However, only one of these three additional strokes results in a patient surviving with residual neurological deficit 1. When calculating net clinical benefit (survival without neurological deficit), tPA remains superior.

High-Risk Patients for Intracranial Hemorrhage

Streptokinase should be preferentially used over tPA in patients with:

• Advanced age (>75 years) 1
• Low body weight (<70 kg) 1
• Uncontrolled hypertension on admission 1
• Prior cerebrovascular disease 1
• Female gender (independent predictor) 1

In these populations, the increased stroke risk with tPA may outweigh the mortality benefit 2.

Optimal Patient Selection for tPA

tPA provides maximum benefit in:

• Patients <75 years old 2
• Anterior wall MI (larger infarct territory) 2
• Treatment within 4 hours of symptom onset 2
• Patients without high bleeding risk factors 2

The European Society of Cardiology guidelines emphasize that for late-presenting patients, fibrin-specific agents like tPA may be more effective than streptokinase 1.

Bleeding Complications Beyond Stroke

Major non-cerebral bleeding occurs in 4-13% of patients with either agent 1. However, tenecteplase (TNK-tPA), a single-bolus variant of tPA, demonstrates significantly lower rates of non-cerebral bleeding compared to accelerated tPA while maintaining equivalent 30-day mortality 1.

Practical Considerations

Streptokinase-Specific Issues

• Hypotension occurs commonly but is usually manageable by temporarily halting infusion, laying the patient flat, or elevating feet 1
• Severe allergic reactions are rare 1
• Never readminister streptokinase as antibodies persist for at least 10 years and can impair activity while increasing allergic reaction risk 1

tPA Advantages

• Can be readministered if re-occlusion or reinfarction occurs, as it does not cause antibody formation 1
• Bolus formulations (reteplase, tenecteplase) facilitate easier administration and reduce medication errors 1

Dosing Protocols

Accelerated tPA regimen: 15 mg IV bolus, then 0.75 mg/kg over 30 minutes (maximum 50 mg), then 0.5 mg/kg over 60 minutes (maximum 35 mg), total dose not to exceed 100 mg, with concurrent IV heparin for 24-48 hours 1

Streptokinase regimen: 1.5 million units in 100 mL over 30-60 minutes, with or without IV heparin 1

Tenecteplase (TNK-tPA): Single weight-adjusted IV bolus (30-50 mg based on body weight), with concurrent IV heparin 1

Common Pitfalls

• Do not use 3-hour tPA infusion protocols—only the accelerated 90-minute regimen demonstrates mortality superiority over streptokinase 1
• Do not give streptokinase to patients with prior streptokinase exposure (within 10 years) 1
• Do not delay treatment for risk stratification—time to treatment is critical, with mortality benefit decreasing by 1.6 deaths per hour of delay per 1000 patients 1
• Do not withhold tPA solely based on age if other risk factors are absent—the mortality benefit persists across age groups 1

Cost Considerations

While tPA costs approximately $1,686 more than streptokinase per patient, this must be weighed against the mortality reduction and the cost of lifelong care for stroke survivors 3. The choice ultimately depends on individual risk assessment, but mortality reduction should take precedence when bleeding risk is acceptable 1.