When to start enoxaparin (low molecular weight heparin) after thrombolysis with Tenecteplase (TNK) in patients with ST-Elevation Myocardial Infarction (STEMI) if immediate revascularization is not planned?

Timing of Enoxaparin After Tenecteplase Thrombolysis in STEMI

Enoxaparin should be administered immediately after tenecteplase thrombolysis in STEMI patients when immediate revascularization is not planned, with an initial IV bolus of 30 mg followed by subcutaneous dosing within minutes of completing the fibrinolytic therapy. 1

Recommended Enoxaparin Dosing Regimen

Initial Dosing

• For patients <75 years old:

  • Initial IV bolus of 30 mg
  • Followed by 1 mg/kg SC every 12 hours (first SC dose shortly after the IV bolus) 1

• For patients ≥75 years old:

  • No initial IV bolus
  • 0.75 mg/kg SC every 12 hours 1

Special Populations

• Patients with impaired renal function (creatinine clearance <30 mL/min):
  • 1 mg/kg SC once daily 1
  • Alternative: Consider unfractionated heparin instead 1

Duration of Anticoagulation

Anticoagulation with enoxaparin should be maintained:

• For a minimum of 48 hours 1
• Preferably for the duration of the index hospitalization 1
• Up to 8 days or until revascularization if performed 1

Evidence Supporting This Approach

The 2025 ACC/AHA guidelines strongly support enoxaparin as the preferred anticoagulant after fibrinolytic therapy in STEMI patients not planned for immediate invasive management 1. This recommendation is based on the ExTRACT-TIMI 25 study, which demonstrated that enoxaparin until hospital discharge (maximum 8 days) was associated with a significant reduction in death or nonfatal recurrent MI through 30 days (9.9% vs 12.0%) compared to UFH 1.

The ENTIRE-TIMI 23 trial showed that enoxaparin with tenecteplase was associated with similar TIMI 3 flow rates as UFH while exhibiting advantages with respect to ischemic events through 30 days (4.4% vs 15.9%, p=0.005) 2.

Pharmacoinvasive Strategy Considerations

If the patient is likely to undergo PCI within 2-24 hours after successful fibrinolysis (pharmacoinvasive approach):

• Continue the enoxaparin regimen 1
• Consider supplemental IV enoxaparin (0.3 mg/kg) at the time of PCI if more than 3 hours have elapsed since the last dose, as anti-Xa levels may be subtherapeutic 3

Monitoring and Safety Considerations

• Monitor for bleeding complications, especially in elderly patients and those with renal impairment
• The risk of major bleeding with enoxaparin after fibrinolysis is comparable to UFH in most studies 2, 4
• Avoid switching between enoxaparin and UFH due to increased risk of bleeding 1
• Consider reduced dosing in high-risk patients (elderly, low body weight, renal impairment) 5

Key Pitfalls to Avoid

1. Delayed administration: Do not delay anticoagulation after fibrinolysis as this may increase the risk of reocclusion
2. Inappropriate dosing in elderly: Remember to omit the IV bolus and reduce the SC dose in patients ≥75 years
3. Failure to adjust for renal function: Always check creatinine clearance and adjust dosing accordingly
4. Switching between anticoagulants: Maintain the same anticoagulant throughout treatment
5. Inadequate duration: Continue anticoagulation for at least 48 hours and preferably until hospital discharge or revascularization

By following these evidence-based recommendations, you can optimize anticoagulation therapy after tenecteplase thrombolysis in STEMI patients, reducing the risk of recurrent ischemic events while maintaining an acceptable safety profile.