What is the administration protocol for low molecular weight heparin (LMWH), such as enoxaparin, in acute myocardial infarction (AMI)?

Administration of Low Molecular Weight Heparin in Acute Myocardial Infarction

For acute myocardial infarction, enoxaparin should be administered at 1 mg/kg subcutaneously every 12 hours for patients with non-ST-elevation MI, or as a 30 mg IV bolus followed by 1 mg/kg subcutaneously every 12 hours for ST-elevation MI receiving fibrinolytic therapy. 1

Clinical Context-Specific Dosing Protocols

ST-Elevation MI (STEMI) with Fibrinolytic Therapy

For patients <75 years old:

• Administer 30 mg IV bolus initially 1, 2
• Follow 15 minutes later with 1 mg/kg subcutaneously every 12 hours 1
• Maximum dose of 100 mg for the first two subcutaneous doses 3
• Continue for up to 8 days or until hospital discharge 3

For patients ≥75 years old:

• Do NOT give the IV bolus due to increased intracranial hemorrhage risk 1, 2
• Administer 0.75 mg/kg subcutaneously every 12 hours 1
• Maximum dose of 75 mg for the first two doses 1

Non-ST-Elevation MI (NSTEMI) or Unstable Angina

• Administer 1 mg/kg subcutaneously every 12 hours 1
• No initial IV bolus required 1
• Continue for 2 to 8 days during acute phase 1
• This regimen demonstrated 24% relative risk reduction at 48 hours compared to unfractionated heparin 1

Primary PCI Without Prior Anticoagulation

• Give 0.5-0.75 mg/kg IV bolus 1
• No subcutaneous dosing needed for isolated PCI 1

PCI After Subcutaneous Enoxaparin Pretreatment

Timing-based supplementation protocol:

• If last subcutaneous dose was <8 hours ago: Give no additional enoxaparin 1, 4
• If last subcutaneous dose was 8-12 hours ago OR only one dose given: Give 0.3 mg IV 1
• If last subcutaneous dose was >12 hours ago: Treat as no prior anticoagulation 1

This approach maintains therapeutic anti-Xa levels (>0.5 IU/mL in 97.6% of patients) without additional monitoring 4.

Critical Dose Adjustments

Severe Renal Impairment (CrCl <30 mL/min)

Reduce dosing frequency to once daily:

• 1 mg/kg subcutaneously every 24 hours (instead of every 12 hours) 1, 2
• This adjustment applies regardless of age or clinical presentation 1
• Failure to adjust increases major bleeding risk substantially 2

Patients Receiving Thrombolytic Therapy with Renal Impairment

• If CrCl <30 mL/min: 1 mg/kg subcutaneously every 24 hours regardless of age 1
• Standard age-based adjustments still apply (no bolus if ≥75 years) 1

Duration of Therapy

Acute phase treatment:

• Minimum 48 hours required 1
• Optimal duration 2-8 days or until hospital discharge 1, 3
• Median treatment duration in major trials was 2.6 days 1

Extended therapy beyond acute phase:

• Long-term outpatient enoxaparin (beyond 8 days) showed no additional benefit over acute phase treatment alone 1
• Maintenance of initial benefit occurred through 43 days, but chronic phase continuation added no further risk reduction 1

Monitoring Requirements

Routine monitoring is NOT required for standard dosing 2. However, specific situations warrant anti-Xa monitoring:

• Severe renal failure (CrCl <30 mL/min) 2
• Obesity 2
• Pregnancy 2

Mandatory platelet monitoring:

• Check platelet counts during treatment to detect heparin-induced thrombocytopenia 2

High-Risk Embolic Situations

For patients at high risk for systemic emboli (large or anterior MI, atrial fibrillation, previous embolus, known LV thrombus):

• Intravenous unfractionated heparin is preferred over subcutaneous enoxaparin 1
• Target aPTT 1.5-2.0 times control (50-70 seconds) 1
• Continue for 48 hours minimum 1

Safety Profile and Bleeding Risk

Major bleeding rates with enoxaparin:

• 1.9% with 1.0 mg/kg every 12 hours dosing 1, 5
• 6.5% with higher 1.25 mg/kg dosing (now abandoned) 1, 5
• Comparable to unfractionated heparin for major bleeding 1, 6
• Minor bleeding (primarily injection site ecchymoses) more common than UFH 6

Critical safety consideration: The ASSENT-3 PLUS trial demonstrated significantly increased intracranial hemorrhage with prehospital enoxaparin in elderly patients, leading to the no-bolus recommendation for patients ≥75 years 1.

Efficacy Evidence

Enoxaparin demonstrated superior outcomes compared to unfractionated heparin:

• 15% relative risk reduction in death/MI/urgent revascularization at 14 days 1
• 19.8% vs 23.3% composite endpoint rate at 30 days (P=0.016) 6
• 27.0% vs 32.2% revascularization rate at 30 days (P=0.001) 6
• Cost savings of $1,172 per patient despite higher drug acquisition cost 1