What is the evidence for administering tenecteplase (TNK) more than 12 hours after symptom onset in patients with myocardial infarction indicated by Q waves on an electrocardiogram (ECG)?

Administration of Tenecteplase (TNK) Beyond 12 Hours in STEMI with Q Waves

Tenecteplase (TNK) should not be routinely administered to patients with STEMI presenting more than 12 hours after symptom onset, even with Q waves present, unless there is clinical evidence of ongoing ischemia, a large area of myocardium at risk, or hemodynamic instability, and primary PCI is not available. 1

Evidence for TNK Administration Beyond 12 Hours

• The benefit of fibrinolytic therapy in patients who present >12 hours after symptom onset has not been well established in clinical trials 1
• Current guidelines provide a Class IIa recommendation (Level of Evidence: C) for fibrinolytic therapy in patients presenting 12-24 hours after symptom onset only when:
  • There is clinical and/or ECG evidence of ongoing ischemia AND
  • A large area of myocardium is at risk or hemodynamic instability is present AND
  • Primary PCI is not available 1, 2
• The presence of Q waves on ECG suggests more advanced infarction and potentially less salvageable myocardium, which may reduce the benefit of late reperfusion therapy 3

Impact of Q Waves on Reperfusion Outcomes

• Patients with baseline Q waves have been shown to have:
  • Smaller myocardial salvage index after reperfusion 4
  • More extensive microvascular obstruction 4
  • Higher 90-day mortality (5.3% vs. 2.1%) 3
  • Higher composite rate of death, CHF, and shock (12.1% vs. 4.8%) 3
• Q waves are an independent prognostic marker that surpasses time from symptom onset in predicting clinical outcomes 3
• Despite reduced efficacy, patients with Q waves still demonstrate substantial myocardial salvage with timely reperfusion 4

Primary PCI vs. Fibrinolysis Beyond 12 Hours

• For patients presenting >12 hours after symptom onset, primary PCI is strongly preferred over fibrinolytic therapy when available 1, 2
• Small randomized trials of patients presenting 12-48 hours after symptom onset have demonstrated that primary PCI can reduce infarct size and improve left ventricular ejection fraction 1
• Transfer to a PCI-capable hospital is reasonable for patients presenting 12-24 hours after symptom onset to reduce infarct size and MACE 1

Considerations When TNK is the Only Option

If primary PCI is unavailable and TNK is being considered beyond 12 hours:

• Carefully assess for absolute contraindications to fibrinolytic therapy 1, 2:
  • Any prior intracranial hemorrhage
  • Known structural cerebral vascular lesion
  • Known malignant intracranial neoplasm
  • Ischemic stroke within 3 months
  • Suspected aortic dissection
  • Active bleeding or bleeding diathesis
  • Significant closed-head or facial trauma within 3 months
  • Severe uncontrolled hypertension
• Evaluate for evidence of ongoing ischemia:
  • Persistent chest pain
  • <50% resolution of ST-segment elevation 1
• Assess the extent of myocardium at risk:
  • Location of infarct (anterior infarctions involve more myocardium) 1
  • Number of leads with ST elevation 1
• Consider hemodynamic status:
  • Presence of heart failure
  • Cardiogenic shock
  • Hemodynamic instability 1

Administration Protocol When TNK is Indicated

If the decision is made to administer TNK beyond 12 hours:

• Administer TNK as a single weight-adjusted IV bolus 1, 5:
  • 30 mg for weight <60 kg
  • 35 mg for 60-69 kg
  • 40 mg for 70-79 kg
  • 45 mg for 80-89 kg
  • 50 mg for ≥90 kg
• Consider 50% dose reduction in patients ≥75 years old to reduce stroke risk 5
• Provide adjunctive therapy:
  • Aspirin (162-325 mg loading dose) 1
  • Clopidogrel (300 mg loading dose for patients <75 years of age, 75 mg for patients >75 years) 1
  • Anticoagulation with unfractionated heparin or enoxaparin 1, 5
• Transfer to a PCI-capable facility after fibrinolytic therapy for routine coronary angiography 1

Important Caveats and Pitfalls

• The "treatment-risk paradox" often results in underutilization of reperfusion therapy in higher-risk patients who might benefit most 1
• Administering TNK outside approved windows without careful patient selection increases bleeding risk, particularly intracranial hemorrhage 2
• Failing to transfer patients to PCI-capable centers after fibrinolytic therapy, even when administered in extended windows 2
• Overlooking absolute contraindications when considering extended window treatment 2