What is the role of tenecteplase (TNK) in myocardial infarction (MI)?

Role of Tenecteplase (TNK) in Myocardial Infarction

Tenecteplase is a preferred fibrin-specific thrombolytic agent for ST-elevation myocardial infarction (STEMI) when primary percutaneous coronary intervention (PCI) cannot be performed in a timely manner, offering the advantage of single-bolus administration with high patency rates. 1

Mechanism and Advantages

Tenecteplase is a genetically engineered variant of alteplase (tPA) with:

• Higher fibrin specificity
• 80-fold greater resistance to plasminogen activator inhibitor-1
• Longer half-life (17-24 minutes vs. 3.5 minutes for alteplase) 2
• Single IV bolus administration (vs. 90-minute infusion for alteplase)
• 85% patency rate (TIMI 2-3 flow at 90 minutes) 1
• Lower rate of non-cerebral bleeding compared to alteplase 3

Indications

Tenecteplase is indicated for:

• STEMI patients presenting within 12 hours of symptom onset 1
• When primary PCI cannot be performed within 90 minutes of first medical contact 1
• Greatest benefit is seen when administered within the first 2-3 hours of symptom onset 1

Dosing

Weight-based single IV bolus administered over 5 seconds:

• 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 1, 4, 5

Adjunctive Therapy

Tenecteplase should always be administered with:

• Aspirin (162-325 mg loading dose) 1
• Clopidogrel (300 mg loading dose for patients <75 years; 75 mg for patients >75 years) 1
• Anticoagulation until revascularization or for duration of hospital stay (up to 8 days) 1
  • Enoxaparin IV followed by SC (preferred over UFH) 1
  • OR weight-adjusted UFH 1

Contraindications

Absolute Contraindications:

• 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
• Intracranial or intraspinal surgery within 2 months
• Severe uncontrolled hypertension 1

Relative Contraindications:

• History of chronic, severe, poorly controlled hypertension
• Significant hypertension on presentation (SBP >180 mmHg or DBP >110 mmHg)
• History of prior ischemic stroke >3 months
• Traumatic or prolonged CPR
• Major surgery within 3 weeks
• Recent internal bleeding 1

Post-Fibrinolysis Management

• Transfer to a PCI-capable center immediately after fibrinolysis 1
• Angiography and PCI of the infarct-related artery is recommended between 2-24 hours after successful fibrinolysis 1
• Rescue PCI is indicated immediately when fibrinolysis has failed (<50% ST-segment resolution at 60-90 min) 1
• Emergency angiography and PCI is indicated in patients with heart failure/shock or recurrent ischemia 1

Clinical Outcomes

• Equivalent 30-day mortality compared to alteplase (approximately 6.2%) 3
• Similar rates of intracranial hemorrhage (0.93% vs. 0.94% with alteplase) 3
• Lower rates of non-cerebral bleeding compared to alteplase (26.43% vs. 28.95%) 3
• May have greater benefit in patients treated >4 hours after symptom onset 3

Common Pitfalls and Caveats

1. Delayed administration: Efficacy decreases significantly with time; administer as soon as possible after STEMI diagnosis, preferably in the pre-hospital setting 1

2. Inappropriate patient selection: Carefully screen for contraindications to avoid bleeding complications 1

3. Failure to provide adjunctive therapy: Always administer with antiplatelet and anticoagulant therapy 1

4. Inadequate post-fibrinolysis care: All patients should be transferred to a PCI-capable center after fibrinolysis 1

5. Inappropriate use in non-STEMI patients: Fibrinolytic therapy should not be administered to patients with only ST-segment depression (except when true posterior STEMI is suspected) due to risk of hemorrhagic stroke 1