What are the guidelines for initiating fibrinolytic therapy in eligible patients?

Guidelines for Initiating Fibrinolytic Therapy in STEMI

Fibrinolytic therapy should be initiated within 30 minutes of first medical contact in eligible STEMI patients when primary PCI cannot be performed within 90-120 minutes of first medical contact. 1

Patient Selection and Timing

Indications

• STEMI patients with symptom onset <12 hours 1
• Consider in patients presenting 12-24 hours after symptom onset with:
  • Clinical and/or ECG evidence of ongoing ischemia
  • Large area of myocardium at risk
  • Hemodynamic instability 1
• Early presenters (<2 hours after symptom onset) with large infarct and low bleeding risk may benefit most 1

Contraindications

Absolute Contraindications 1

• Previous intracranial hemorrhage or stroke of unknown origin at any time
• Ischemic stroke in preceding 6 months
• Central nervous system damage/neoplasms/AV malformation
• Recent major trauma/surgery/head injury (within 3 weeks)
• Gastrointestinal bleeding within past month
• Known bleeding disorder
• Aortic dissection
• Non-compressible punctures in past 24 hours

Relative Contraindications 1

• TIA in preceding 6 months
• Oral anticoagulant therapy
• Pregnancy or within 1 week postpartum
• Refractory hypertension (SBP >180 mmHg and/or DBP >110 mmHg)
• Advanced liver disease
• Infective endocarditis
• Active peptic ulcer
• Prolonged or traumatic resuscitation

Time Targets

• Pre-hospital setting: within 30 minutes of first medical contact 1
• In-hospital setting: within 30 minutes of arrival (door-to-needle time) 1
• Not recommended beyond 24 hours after symptom onset 2

Medication Selection and Dosing

Preferred Agents

• Fibrin-specific agents are recommended over non-fibrin specific agents 1
  • Tenecteplase (TNK-tPA): Single IV weight-based bolus
    • 30 mg if <60 kg
    • 35 mg if 60-69 kg
    • 40 mg if 70-79 kg
    • 45 mg if 80-89 kg
    • 50 mg if ≥90 kg
  • Reteplase (rPA): Two 10-unit IV boluses given 30 minutes apart
  • Alteplase (tPA): 90-minute weight-based infusion
    • 15 mg IV bolus
    • 0.75 mg/kg over 30 min (up to 50 mg)
    • 0.5 mg/kg over 60 min (up to 35 mg)

Required Adjunctive Therapies

Antiplatelet Therapy 1

• Aspirin: 150-300 mg oral loading dose (or 80-150 mg IV if oral not possible)
  • Followed by 75-100 mg daily maintenance
• Clopidogrel: Loading dose followed by maintenance
  • 300 mg loading dose (75 mg for elderly >75 years)
  • 75 mg daily maintenance
• Prasugrel and ticagrelor should NOT be used with fibrinolysis

Anticoagulation 1

• Required until revascularization or for duration of hospital stay (up to 8 days)
• Preferred options:
  • Enoxaparin: 30 mg IV bolus followed by 1 mg/kg SC every 12 hours (preferred over UFH)
  • Unfractionated heparin (UFH): Weight-adjusted IV bolus (60 U/kg, max 4000 U) followed by infusion (12 U/kg/h, max 1000 U/h) with target aPTT 1.5-2.0 times control
  • Fondaparinux: For patients receiving streptokinase - 2.5 mg IV bolus followed by 2.5 mg SC once daily

Post-Fibrinolysis Management

Transfer Protocol

• All patients should be transferred to a PCI-capable center immediately after fibrinolysis 1

Rescue PCI Indications 1

• Failed fibrinolysis (<50% ST-segment resolution at 60-90 minutes)
• Hemodynamic or electrical instability
• Worsening ischemia
• Heart failure/cardiogenic shock

Routine Angiography Timing

• For stable patients after successful fibrinolysis: 2-24 hours 1

Common Pitfalls to Avoid

1. Delayed administration - Every 30-minute delay reduces benefits; aim for rapid door-to-needle times
2. Using non-fibrin specific agents - Fibrin-specific agents have better efficacy and safety profiles
3. Readministration of streptokinase - Avoid due to antibody formation and risk of allergic reactions 1
4. Omitting adjunctive antiplatelet/anticoagulant therapy - These are essential components of the regimen
5. Administering fibrinolytics to patients with ST depression - Not indicated except when true posterior STEMI is suspected 1
6. Failing to transfer to PCI-capable center - All patients should be transferred for potential rescue PCI
7. Missing contraindications - Careful screening for bleeding risk is essential before administration

By following these guidelines systematically, clinicians can optimize the benefits of fibrinolytic therapy while minimizing risks in eligible STEMI patients.