What is the role of heparin (unfractionated heparin (UFH) or low molecular weight heparin (LMWH)) in the management of Non-ST-Elevation Myocardial Infarction (NSTEMI)?

Heparin in NSTEMI

Anticoagulation with either unfractionated heparin (UFH) or low molecular weight heparin (LMWH, specifically enoxaparin) is essential in NSTEMI management, with the choice depending on your planned management strategy: enoxaparin is preferred for conservative management, while either enoxaparin or UFH are reasonable for planned invasive approaches. 1, 2

Initial Anticoagulation Strategy

All NSTEMI patients require immediate parenteral anticoagulation unless contraindicated. 2, 3 The selection between agents should be based on:

For Conservative (Non-Invasive) Management

• Enoxaparin 1 mg/kg subcutaneously every 12 hours is the preferred agent (Class IIa, LOE A) 1, 2
• Fondaparinux 2.5 mg subcutaneously once daily is a reasonable alternative (Class IIa, LOE B) 1
• Both options demonstrate similar or improved composite outcomes (death, MI, recurrent angina) compared to UFH, with enoxaparin showing particular superiority in multiple meta-analyses 1

For Planned Early Invasive Management (PCI)

• Either enoxaparin or UFH are equally reasonable choices (Class IIa, LOE A) 1, 2
• The key advantage of enoxaparin is predictable anticoagulation without need for aPTT monitoring 1
• UFH allows more precise titration and immediate reversibility if needed 1

Enoxaparin Dosing Specifics

Standard dosing: 1 mg/kg subcutaneously every 12 hours 2

Age-based modifications:

• Patients <75 years: Consider 30 mg IV bolus followed by 1 mg/kg SC every 12 hours 1, 4
• Patients ≥75 years: 0.75 mg/kg SC every 12 hours without IV bolus 1, 4

Renal dosing (critical):

• Creatinine clearance <30 mL/min: Reduce to 1 mg/kg once daily 1, 2, 4
• Consider UFH as alternative in severe renal impairment for easier monitoring 1

Bridging to Cardiac Catheterization

If proceeding to PCI on enoxaparin, timing matters: 2

• Last dose <8 hours ago: No additional anticoagulation needed 2
• Last dose 8-12 hours ago OR <2 therapeutic doses given: Administer 0.3 mg/kg IV enoxaparin at catheterization 2

Special Populations

High Bleeding Risk Patients

• Fondaparinux (Class IIa, LOE B) or bivalirudin (Class IIa, LOE A) are preferred over UFH (Class IIb, LOE C) 1
• These agents demonstrate reduced bleeding complications while maintaining efficacy 1, 5

Renal Insufficiency

• Bivalirudin or UFH are preferred (Class IIb, LOE A) as they don't require renal dose adjustment 1
• If using enoxaparin, mandatory dose reduction to once daily dosing 2, 4

Hepatic Dysfunction

• Elevated transaminases alone are NOT a contraindication to enoxaparin 4
• Exercise extreme caution only when INR ≥1.5 (indicating synthetic dysfunction, not just hepatocellular injury) 4
• UFH may be preferred in severe hepatic failure for easier monitoring via aPTT 4

Critical Pitfalls to Avoid

Never switch between anticoagulants mid-treatment: Transitioning from enoxaparin to UFH or vice versa significantly increases bleeding risk (Class III, LOE C) 1, 2

Fondaparinux requires special handling at PCI: It increases catheter thrombosis risk when used alone and requires co-administration of UFH during the procedure, offering no advantage over UFH alone (Class IIb, LOE A) 1, 2

Discontinue anticoagulation after uncomplicated PCI: Parenteral anticoagulation should stop immediately post-procedure unless compelling indication exists 2, 3

Evidence Quality Considerations

The superiority of enoxaparin over UFH in conservative management is supported by 11 randomized trials and 7 meta-analyses demonstrating improved composite outcomes, though with increased minor bleeding 1. The ESSENCE and TIMI 11B trials (7,081 patients combined) specifically demonstrated significant reduction in death or MI with enoxaparin 1. More recent data from the INTERACT trial showed enoxaparin reduced major bleeding by 60% compared to UFH when combined with GP IIb/IIIa inhibitors 1.

The practical advantage of enoxaparin is elimination of aPTT monitoring, which is notoriously unreliable in ACS due to reagent variability between institutions 1, 6. UFH also paradoxically stimulates platelet aggregation, potentially promoting further clot formation 6.

Institutional Implementation

Each institution should establish a consistent anticoagulation protocol to minimize medication errors and avoid double anticoagulation when multiple providers are involved 1. The choice should weigh established efficacy, bleeding risk, cost, familiarity with dosing (especially for PCI), anticipated need for surgery, and ability to reverse anticoagulation if bleeding occurs 1.