What is the preferred anticoagulant, Low Molecular Weight Heparin (LMWH) vs Unfractionated Heparin (UFH) vs Fondaparinux, in patients with acute coronary syndrome?

Anticoagulation Choice in Acute Coronary Syndromes

For patients with ACS, the preferred anticoagulant depends on the clinical scenario: enoxaparin (LMWH) is preferred for initial medical management in both NSTE-ACS and STEMI due to superior or equivalent efficacy with practical advantages; UFH remains the standard for patients proceeding to PCI due to reversibility and ACT monitoring; fondaparinux offers the best bleeding profile for conservative management but is contraindicated as sole support for PCI due to catheter thrombosis risk. 1

Clinical Scenario-Based Algorithm

NSTE-ACS with Conservative (Non-Invasive) Strategy

• Fondaparinux 2.5 mg subcutaneous daily is the preferred agent for patients managed conservatively, as it demonstrated equivalent ischemic outcomes to enoxaparin but with significantly reduced major bleeding in the OASIS-5 trial 1
• Enoxaparin 1 mg/kg subcutaneous every 12 hours is an equally reasonable alternative, with proven superiority over UFH in reducing death/MI/recurrent angina (16.6% vs 19.6% at 14 days) in the ESSENCE trial 1
• UFH is acceptable but offers no advantage over LMWH in this setting, with meta-analyses showing no significant difference in death or MI (2.2% vs 2.3%) 1

NSTE-ACS with Early Invasive Strategy (Planned PCI)

• Either enoxaparin or UFH are reasonable first-line choices when PCI is planned 1
• UFH has traditionally been preferred to support PCI due to ACT-guided dosing during the procedure and reversibility with protamine 1
• If enoxaparin was started initially, dosing adjustments are needed: give 0.3 mg/kg IV if last subcutaneous dose was 8-12 hours prior; no additional dose if within 8 hours 1
• Fondaparinux should NOT be used as sole anticoagulation for PCI due to increased catheter thrombosis risk (0.9% vs 0.3% with enoxaparin); if used, must add UFH 1

STEMI with Fibrinolytic Therapy

• Enoxaparin is superior to UFH when combined with fibrinolytics, with dosing adjusted by age: 1
  • Age <75 years: 30 mg IV bolus, then 1 mg/kg subcutaneous every 12 hours (maximum 100 mg first two doses)
  • Age ≥75 years: no bolus, 0.75 mg/kg subcutaneous every 12 hours (maximum 75 mg first two doses)
• Fondaparinux 2.5 mg IV bolus followed by 2.5 mg subcutaneous daily is an alternative, with demonstrated reduction in death or reinfarction at 30 days compared to usual care in OASIS-6 2

STEMI with Primary PCI

• UFH remains the standard anticoagulant for primary PCI due to immediate onset, ACT monitoring capability, and protamine reversibility 1
• Bivalirudin with prolonged full-dose post-PCI infusion (2-4 hours) showed superiority to UFH in the BRIGHT-4 trial, reducing 30-day death/major bleeding and stent thrombosis 1

Key Pharmacologic Distinctions

LMWH (Enoxaparin) Advantages

• More predictable anticoagulation without need for aPTT monitoring due to reduced plasma protein binding 3, 4
• Lower risk of heparin-induced thrombocytopenia (64% reduction) compared to UFH 5
• Subcutaneous administration once or twice daily versus continuous UFH infusion 3, 4
• Meta-analysis of 7 trials (11,092 patients) showed LMWH reduced MI (RR 0.83) and need for revascularization (RR 0.88) compared to UFH 5

UFH Advantages

• Immediate reversibility with protamine for patients at high bleeding risk or needing urgent procedures 3
• ACT-guided dosing during PCI allows real-time adjustment 1
• Preferred in severe renal insufficiency (CrCl <30 mL/min) as LMWH accumulates renally 1, 3

Fondaparinux Advantages

• Lowest bleeding risk among all anticoagulants in ACS, with superior bleeding profile versus enoxaparin in OASIS-5 1, 2
• Once-daily dosing with predictable pharmacokinetics 2
• Contraindicated if CrCl <30 mL/min 1

Critical Pitfalls to Avoid

• Never use fondaparinux alone for PCI support—the 0.9% catheter thrombosis rate mandates adding UFH if PCI becomes necessary 1
• Do not abruptly discontinue anticoagulation—premature cessation causes rebound thrombin activation with greatest reinfarction risk at 4-8 hours 1
• Adjust enoxaparin dosing in renal dysfunction: reduce to 1 mg/kg daily if CrCl <30 mL/min; consider UFH if CrCl <15 mL/min 1, 3
• Account for timing when bridging from enoxaparin to PCI—inappropriate dosing increases bleeding without added efficacy 1
• Monitor for increased minor bleeding with LMWH during vascular instrumentation, though major bleeding rates are equivalent to UFH 6

Duration of Therapy

• Continue anticoagulation until revascularization (PCI or CABG) is performed 1
• For medical management, typical duration is 2-8 days (median 2.6 days in ESSENCE trial) 1
• No proven benefit for prolonged outpatient LMWH beyond acute phase in ACS, unlike VTE treatment 1, 3