When to give streptokinase (thrombolytic agent) or heparin (anticoagulant) in acute myocardial infarction (heart attack)?

Decision Algorithm for Streptokinase vs Heparin in Myocardial Infarction

Primary Decision: Reperfusion Strategy First

The choice between streptokinase and heparin is not an either/or decision—they serve different roles and are often used together in acute myocardial infarction management. The critical first decision is whether the patient can receive timely primary PCI, which determines the entire treatment pathway 1.

Step 1: Assess PCI Availability (Time-Critical)

If primary PCI can be performed by an experienced team within 90-120 minutes of first medical contact, proceed directly to PCI—this is the preferred reperfusion strategy 1, 2.

If primary PCI cannot be performed within this timeframe, initiate fibrinolytic therapy (streptokinase or preferably a fibrin-specific agent) immediately 1.

• For patients presenting very early (<2 hours) with large infarcts and low bleeding risk, consider fibrinolysis if PCI delay exceeds 90 minutes 1
• Prehospital fibrinolysis should be started when possible 1

Step 2: When to Give Streptokinase

Streptokinase is indicated when:

• Primary PCI is not available within the critical time window AND
• The patient presents within 12 hours of symptom onset AND
• No contraindications to fibrinolysis exist 1

Dosing: 1.5 million units IV over 30-60 minutes 1

Key contraindications to streptokinase specifically:

• Prior streptokinase or anistreplase administration (antibodies persist for at least 10 years) 1
• All standard fibrinolytic contraindications apply 1

Important caveat: Fibrin-specific agents (tenecteplase, alteplase, reteplase) are recommended over streptokinase when available, as they provide superior outcomes 1, 2. Streptokinase is primarily used when cost or availability limit access to newer agents 1.

Step 3: When to Give Heparin

Heparin plays different roles depending on the reperfusion strategy chosen:

A. With Fibrin-Specific Agents (Alteplase, Tenecteplase, Reteplase)

Mandatory: IV unfractionated heparin (UFH) is required as adjunctive therapy 1.

• Dosing: Weight-adjusted IV bolus followed by infusion targeting aPTT 50-75 seconds (or 60-85 seconds per some protocols) for 24-48 hours 1
• Rationale: Fibrin-specific agents have shorter half-lives and require concurrent anticoagulation to prevent reocclusion 1

B. With Streptokinase

Not routinely recommended for IV administration in the first 6 hours 1.

• Subcutaneous heparin (7,500-12,500 U twice daily) may be given starting 12 hours after streptokinase until patient is fully ambulatory 1
• Exception: IV heparin IS indicated with streptokinase for patients at high risk of systemic embolism (large anterior MI, atrial fibrillation, LV thrombus, prior embolic event) 1
• Evidence: Large trials (ISIS-3, International Study Group) showed subcutaneous heparin with streptokinase provided only marginal benefit (5 fewer deaths per 1000 patients) with increased bleeding risk 1, 3

C. With Primary PCI

Mandatory: High-dose IV heparin during the procedure 1.

• Dosing: 100 U/kg bolus (60 U/kg if using GPIIb/IIIa inhibitors) 1
• Target ACT: 250-350 seconds (200-250 seconds with GPIIb/IIIa inhibitors) 1

D. Without Any Reperfusion Therapy

Recommended: Anticoagulation should be initiated 1.

• Preferred: Enoxaparin or fondaparinux over UFH 1
• Alternative: UFH if low-molecular-weight heparins unavailable 1
• Historical data: Pre-reperfusion era trials showed 17% mortality reduction and 22% reduction in reinfarction with heparin, though these patients did not receive aspirin 1

Step 4: Mandatory Adjunctive Antiplatelet Therapy

Regardless of whether streptokinase or heparin is chosen, ALL patients must receive:

• Aspirin: 150-325 mg orally (chewed, not enteric-coated) or 250-500 mg IV if oral not possible, then 75-100 mg daily 1, 2
• Clopidogrel: Loading dose 300 mg (600 mg preferred for PCI) if age <75 years; 75 mg if age ≥75 years 1, 2

Step 5: Preferred Anticoagulation Regimen with Fibrinolysis

The European Society of Cardiology recommends enoxaparin over UFH when using fibrinolytic therapy 1.

• Enoxaparin dosing: IV bolus followed by subcutaneous dosing every 12 hours 1
• Duration: Until revascularization or up to 8 days of hospitalization 1
• Alternative for streptokinase specifically: Fondaparinux (IV bolus followed by subcutaneous dose 24 hours later) 1

Step 6: Post-Fibrinolytic Management

All patients receiving fibrinolytic therapy (streptokinase or other agents) require:

• Transfer to PCI-capable center immediately after fibrinolysis 1, 2
• Rescue PCI if fibrinolysis fails (<50% ST-segment resolution at 60 minutes) 1, 2
• Routine angiography 3-24 hours after successful fibrinolysis (optimal timing for stable patients) 1, 2

Common Pitfalls to Avoid

Do not give IV heparin routinely with streptokinase in the first 6 hours—this is a Class III recommendation (harmful) unless the patient has high embolic risk 1. The GUSTO trial demonstrated that IV heparin with streptokinase was not superior to subcutaneous heparin and increased bleeding 1.

Do not re-administer streptokinase if reocclusion occurs—use alteplase or mechanical intervention instead, as antibodies render repeat streptokinase ineffective and dangerous 1.

Do not delay fibrinolysis to start heparin—aspirin and the fibrinolytic agent should be given immediately; heparin timing depends on the specific agent used 1.

Monitor aPTT closely when using UFH—subtherapeutic anticoagulation increases reocclusion risk while supratherapeutic levels increase bleeding 1.

Avoid subclavian or internal jugular venous access during fibrinolytic therapy—use upper extremity vessels accessible to manual compression 4.

Summary Algorithm

1. Can PCI be done in 90-120 minutes? → YES: Give heparin + aspirin + clopidogrel, proceed to PCI 1
2. Can PCI be done in 90-120 minutes? → NO: Give fibrinolytic therapy + aspirin + clopidogrel 1
3. Which fibrinolytic? → Prefer tenecteplase/alteplase/reteplase over streptokinase 1, 2
4. If using fibrin-specific agent: → Give IV UFH (or preferably enoxaparin) concurrently 1
5. If using streptokinase: → Give subcutaneous heparin starting 12 hours later (or IV heparin only if high embolic risk) 1
6. All patients: → Transfer to PCI center for angiography within 3-24 hours 1, 2