In STEMI, is tenecteplase or enoxaparin given first?

Administration Order of Tenecteplase and Enoxaparin in STEMI

In STEMI management, tenecteplase should be administered first, followed by enoxaparin as adjunctive anticoagulant therapy. This sequence is based on established guidelines for fibrinolytic therapy in ST-elevation myocardial infarction.

Rationale for Administration Sequence

Tenecteplase First

• Tenecteplase is the primary reperfusion agent that directly targets the occluding thrombus in the coronary artery
• It is administered as a single weight-based IV bolus over 5 seconds 1
• The goal is to initiate treatment as soon as possible after symptom onset to achieve rapid reperfusion

Enoxaparin Second

• Enoxaparin serves as adjunctive anticoagulation therapy to prevent reocclusion and recurrent thrombotic events
• It is administered after tenecteplase, typically as an initial IV bolus of 30 mg followed by subcutaneous dosing 2

Evidence-Based Protocol

The European Society of Cardiology guidelines clearly outline this sequence in their fibrinolytic therapy protocol 2:

1. First: Administer tenecteplase as a single IV bolus with weight-based dosing:

   • 30 mg if <60 kg
   • 35 mg if 60 to <70 kg
   • 40 mg if 70 to <80 kg
   • 45 mg if 80 to <90 kg
   • 50 mg if ≥90 kg

2. Second: Administer enoxaparin:

   • Initial IV bolus of 30 mg
   • Followed by 1 mg/kg subcutaneously every 12 hours (maximum 100 mg for first two doses)
   • Continue for the duration of hospital stay (maximum 8 days) or until revascularization 2

Special Considerations

• Age ≥75 years: Omit the initial IV bolus of enoxaparin and reduce subcutaneous dose to 0.75 mg/kg every 12 hours 2, 3
• Renal impairment: For patients with CrCl <30 mL/min, reduce enoxaparin to 1 mg/kg once daily 4
• Timing: The TRANSFER-AMI study showed that the median time to administration of tenecteplase from symptom onset was approximately 2 hours, with enoxaparin administered afterward 2

Clinical Outcomes

This sequence has been validated in multiple clinical trials:

• The ENTIRE-TIMI 23 trial showed that tenecteplase followed by enoxaparin resulted in better outcomes than tenecteplase with unfractionated heparin, with death/recurrent MI reduced from 15.9% to 4.4% at 30 days 5
• The ExTRACT-TIMI 25 trial demonstrated that this sequence significantly reduced the composite endpoint of death and recurrent MI compared to tenecteplase followed by unfractionated heparin 6, 4

Potential Pitfalls to Avoid

1. Delayed administration: Do not delay tenecteplase administration while waiting to prepare enoxaparin
2. Incorrect dosing: Ensure weight-based dosing of tenecteplase and appropriate adjustment of enoxaparin for elderly patients and those with renal impairment
3. Contraindications: Always check for contraindications to fibrinolytic therapy before administration
4. Monitoring: After administration of both medications, monitor for signs of bleeding, especially intracranial hemorrhage, which is more common in elderly patients 3

Following this sequence of tenecteplase first, followed by enoxaparin, provides optimal reperfusion therapy while minimizing the risk of reocclusion and recurrent ischemic events in STEMI patients.