What is the order of administration of streptokinase and enoxaparin (low molecular weight heparin) in the management of ST elevation myocardial infarction (STEMI)?

Order of Administration for Streptokinase and Enoxaparin in STEMI

In ST-elevation myocardial infarction (STEMI), streptokinase should be administered first, followed by enoxaparin, with the enoxaparin given as an intravenous bolus followed by subcutaneous injections. 1

Recommended Administration Sequence

1. Initial Streptokinase Administration:

   • Administer streptokinase 1.5 million units over 30-60 minutes intravenously 1
   • Start immediately after STEMI diagnosis when primary PCI cannot be performed in a timely manner 1

2. Antiplatelet Therapy (Given Concurrently):

   • Aspirin: 150-325 mg oral loading dose (chewable, non-enteric coated) or 250-500 mg IV if oral ingestion not possible 1
   • Clopidogrel: 300 mg loading dose (for patients <75 years) or 75 mg (for patients >75 years) 1

3. Enoxaparin Administration:

   • After streptokinase infusion, administer enoxaparin as follows 1, 2:
     • Initial IV bolus of 30 mg
     • Followed 15 minutes later by subcutaneous injection of 1 mg/kg every 12 hours
     • Continue for the duration of hospitalization (up to 8 days) or until revascularization

Special Considerations

• Dosage Adjustments:

  • For patients ≥75 years: Omit the initial IV bolus and reduce subcutaneous dose to 0.75 mg/kg every 12 hours 3
  • For patients with renal impairment (CrCl <30 mL/min): Reduce to 1 mg/kg once daily 3

• Timing Considerations:

  • Fibrinolytic therapy should be initiated as soon as possible after STEMI diagnosis when PCI cannot be performed within 120 minutes 1, 2
  • The efficacy of thrombolysis decreases significantly with time, with greatest benefit when given within the first 3 hours 2

Evidence and Rationale

The European Society of Cardiology guidelines clearly recommend that when fibrinolysis is the reperfusion strategy, enoxaparin is the preferred anticoagulant to be administered after streptokinase 1. This sequence is supported by studies showing improved outcomes compared to unfractionated heparin.

The ExTRACT-TIMI 25 trial demonstrated that enoxaparin was significantly more effective than unfractionated heparin in patients receiving fibrinolytic therapy, with lower rates of death and recurrent MI 3, 4. This benefit was observed regardless of the fibrinolytic agent used, including streptokinase 4.

Post-Administration Management

After administration of streptokinase and enoxaparin:

• All patients should be transferred immediately to a PCI-capable center 1, 2
• Coronary angiography and PCI of the infarct-related artery should be performed between 2-24 hours after successful fibrinolysis 1
• Monitor for signs of failed fibrinolysis (less than 50% ST-segment resolution at 60-90 minutes) and be prepared for rescue PCI if needed 1

The proper sequencing of streptokinase followed by enoxaparin is critical for achieving optimal outcomes in STEMI patients when primary PCI cannot be performed in a timely manner.