What is the recommended dose of enoxaparin (low molecular weight heparin) for a patient with acute coronary syndrome and impaired renal function (creatinine clearance of 31 mL/min)?

Enoxaparin Dosing for ACS with CrCl 31 mL/min

For a patient with acute coronary syndrome and creatinine clearance of 31 mL/min, reduce enoxaparin to 1 mg/kg subcutaneously once daily (every 24 hours) instead of the standard twice-daily dosing. 1

Dosing Regimen

Initial Therapy

• Administer 1 mg/kg subcutaneously every 24 hours for patients with CrCl <30 mL/min 1
• This represents a 50% reduction in total daily dose compared to standard dosing (which is 1 mg/kg every 12 hours) 1
• The 2025 ACC/AHA/SCAI guidelines explicitly state this dose reduction for CrCl <30 mL/min in the ACS setting 1

If Fibrinolytic Therapy is Used

• Give 1 mg/kg subcutaneously every 24 hours regardless of age when CrCl <30 mL/min 1
• Do not administer the initial IV bolus that would normally be given to younger patients 1
• Do not use the age-adjusted dosing (0.75 mg/kg for elderly) - the renal adjustment supersedes age-based adjustments 1

If PCI is Planned

• For patients already on subcutaneous enoxaparin who proceed to PCI, timing of last dose determines additional dosing 1:
  • If last dose was 8-12 hours prior: give 0.3 mg IV 1
  • If last dose was within 8 hours: no additional enoxaparin needed 1
  • If only one subcutaneous dose given: give 0.3 mg IV 1

Rationale for Dose Reduction

Pharmacokinetic Evidence

• Enoxaparin clearance is reduced by 44% in patients with severe renal impairment (CrCl <30 mL/min) 2
• Drug accumulation occurs with standard dosing, leading to significantly elevated anti-Xa levels 2, 3
• Renal function is the most influential covariate affecting enoxaparin clearance, with a strong linear correlation (R=0.85, P<0.001) 4

Bleeding Risk

• Patients with CrCl <30 mL/min have 2.25 times higher odds of major bleeding (OR 2.25,95% CI 1.19-4.27) when receiving standard doses 4
• Therapeutic-dose enoxaparin without adjustment increases major bleeding nearly 4-fold (8.3% vs 2.4%; OR 3.88) 4
• Dose reduction eliminates this excess bleeding risk (0.9% vs 1.9%; OR 0.58) 4

Critical Considerations

Do Not Switch Anticoagulants

• Never switch between enoxaparin and unfractionated heparin once therapy is initiated, as this significantly increases bleeding risk 1, 4
• If you have concerns about enoxaparin in renal impairment, choose UFH from the outset rather than switching 1

Alternative: Unfractionated Heparin

• UFH is a reasonable alternative that does not require renal dose adjustment 1, 4
• Dosing: 60 IU/kg IV bolus (max 4000 IU), then 12 IU/kg/h infusion (max 1000 IU/h) adjusted to aPTT 60-80 seconds 1
• Consider UFH if you anticipate the need for urgent invasive procedures or if bleeding risk is particularly high 1

Avoid Fondaparinux

• Fondaparinux is absolutely contraindicated when CrCl <30 mL/min 1, 4
• Do not use fondaparinux as an alternative in this patient 1

Monitoring Considerations

Anti-Xa Monitoring

• Consider monitoring peak anti-Xa levels in patients with CrCl <30 mL/min to prevent drug accumulation 4
• Check levels 4 hours after administration 4
• Target therapeutic range: 0.5-1.0 IU/mL 4
• However, routine monitoring is not required in most cases if the dose is appropriately adjusted 1

Clinical Monitoring

• Monitor closely for signs of bleeding (major or minor) 5
• Increasing age further compounds bleeding risk beyond renal impairment alone (OR 1.57 per decade) 5
• Concomitant antiplatelet therapy (especially clopidogrel) dramatically increases bleeding risk (OR 7.70) 5

Common Pitfalls to Avoid

• Do not use standard twice-daily dosing (1 mg/kg every 12 hours) in patients with CrCl <30 mL/min - this leads to dangerous accumulation 1, 2
• Do not round the CrCl threshold - a CrCl of 31 mL/min is close enough to 30 mL/min that dose reduction is warranted given individual variability in renal function 2
• Do not forget to document actual body weight - 9% of ACS patients receiving enoxaparin lack weight documentation, leading to dosing errors 5
• Do not exceed 100 mg per dose even in obese patients when using standard dosing (though this cap may not apply to the once-daily regimen in renal impairment) 1