What is the initial pharmacotherapy before administering streptokinase (thrombolytic agent)?

Initial Pharmacotherapy Before Administering Streptokinase

Before administering streptokinase, patients should receive aspirin (150-325 mg orally or 250-500 mg IV if oral ingestion is not possible) and clopidogrel (300 mg loading dose if ≤75 years; 75 mg if >75 years), along with anticoagulation therapy using weight-adjusted unfractionated heparin, enoxaparin, or fondaparinux. 1, 2

Antiplatelet Therapy

Aspirin

• Give immediately upon diagnosis of STEMI
• Dosage: 150-325 mg orally (chewable/non-enteric coated preferred) or 250-500 mg IV if oral route not feasible
• Mechanism: Inhibits thromboxane A2 production, providing immediate antithrombotic effect
• Evidence: ISIS-2 trial demonstrated 23% reduction in 35-day mortality with aspirin alone and 42% reduction when combined with streptokinase 1, 2

Clopidogrel

• Administer concurrently with aspirin
• Dosage:
  • Age ≤75 years: 300 mg loading dose
  • Age >75 years: 75 mg (no loading dose)
• Evidence: CLARITY-TIMI 28 and COMMIT trials showed reduced risk of cardiovascular events and overall mortality when clopidogrel was added to aspirin as adjunct to fibrinolytic therapy 1, 2

Important note: Prasugrel and ticagrelor have not been studied as adjuncts to fibrinolysis and should not be given 1

Anticoagulation Therapy

Anticoagulation should be administered before streptokinase and continued until revascularization (if performed) or for at least 48 hours or duration of hospital stay (up to 8 days) 1.

Options for anticoagulation (in order of preference):

1. With streptokinase specifically:

   • Fondaparinux: IV bolus followed by subcutaneous dose 24 hours later
     • Evidence: OASIS-6 trial showed superiority to placebo or UFH in preventing death and reinfarction, especially with streptokinase 1

2. If fondaparinux unavailable:

   • Enoxaparin:
     • Age ≤75 years: 30 mg IV bolus followed 15 minutes later by subcutaneous dose
     • Age >75 years: No IV bolus, start with reduced subcutaneous dose
     • Evidence: ExTRACT-TIMI 25 trial showed reduced risk of death and reinfarction compared to UFH 1

3. Alternative option:

   • Unfractionated heparin (UFH): 60 U/kg IV bolus (maximum 4000 U) followed by IV infusion of 12 U/kg/hr (maximum 1000 U/hr)
     • Target aPTT: 50-70 seconds or 1.5-2.0 times control
     • Monitor at 3,6,12, and 24 hours 2

Clinical Pearls and Pitfalls

Timing Considerations

• Initiate all adjunctive therapies immediately upon diagnosis of STEMI
• Administer streptokinase within 12 hours of symptom onset, with greatest benefit within the first 3 hours 2

Contraindications to Consider

• Prior streptokinase exposure (within past 6 months) is an absolute contraindication due to risk of allergic reactions 2
• Streptokinase antibodies persist for at least 10 years, impairing activity and increasing allergic reaction risk 2, 3

Monitoring for Complications

• Hypotension is common during streptokinase infusion - monitor blood pressure closely
• Bleeding risk is increased with combination therapy - observe for signs of hemorrhage
• Allergic reactions may occur with streptokinase - be prepared to treat with antihistamines if needed

Avoiding Common Pitfalls

1. Do not delay antiplatelet therapy while waiting for streptokinase preparation
2. Do not administer GP IIb/IIIa inhibitors with streptokinase as there is no evidence of benefit and bleeding risk may increase 1
3. Do not readminister streptokinase to patients previously exposed (antibodies persist for years) 2, 3
4. Do not use prasugrel or ticagrelor as adjuncts to fibrinolysis 1

By following this protocol for initial pharmacotherapy before streptokinase administration, you can maximize the efficacy of thrombolytic therapy while minimizing the risk of complications, ultimately improving patient outcomes in terms of mortality, morbidity, and quality of life.