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

Anticoagulation Choice in Acute Coronary Syndrome

For NSTE-ACS managed conservatively, fondaparinux 2.5 mg subcutaneous daily is the preferred agent due to equivalent ischemic outcomes with significantly reduced major bleeding compared to enoxaparin, while for patients proceeding to early PCI, enoxaparin 1 mg/kg subcutaneous every 12 hours is preferred over UFH based on superior efficacy in reducing death/MI/recurrent angina. 1

Conservative Management Strategy (No Early PCI Planned)

Fondaparinux is the first-line choice for NSTE-ACS patients managed medically, as demonstrated in the OASIS-5 trial with equivalent ischemic outcomes but significantly reduced major bleeding versus enoxaparin. 1 The 2020 ESC Guidelines recommend fondaparinux specifically when logistical constraints prevent timely PCI transfer. 2

• Dosing: 2.5 mg subcutaneous once daily 1
• Contraindication: CrCl <30 mL/min 1
• Critical caveat: Never use fondaparinux alone if PCI becomes necessary—the 0.9% catheter thrombosis rate mandates adding UFH bolus at time of catheterization 1

Enoxaparin is an equally reasonable alternative with proven superiority over UFH in the ESSENCE trial (16.6% vs 19.6% death/MI/recurrent angina at 14 days). 1

• Dosing: 1 mg/kg subcutaneous every 12 hours 1
• Renal adjustment: Reduce to 1 mg/kg daily if CrCl <30 mL/min; consider UFH if CrCl <15 mL/min 1

UFH is acceptable but offers no advantage over LMWH in conservative management, with meta-analyses showing no significant difference in death or MI (2.2% vs 2.3%). 1

Early Invasive Strategy (PCI Planned)

Enoxaparin is preferred over UFH based on two head-to-head trials demonstrating superiority for the combined endpoint of death/MI/recurrent angina, with results confirmed at 1-year follow-up. 2, 1 The 2011 ACC/AHA Guidelines acknowledge that enoxaparin offers practical advantages including once versus twice daily dosing and lower HIT risk. 2

UFH remains standard for primary PCI due to immediate onset, ACT monitoring capability during the procedure, and protamine reversibility for high bleeding risk patients. 1 The 2020 ESC Guidelines recommend weight-adjusted UFH bolus during PCI (70-100 IU/kg, or 50-70 IU/kg with GP IIb/IIIa inhibitor; ACT target 250-350 seconds). 2

• Do not cross over between UFH and LMWH—the ESC explicitly recommends against switching anticoagulants. 2

STEMI-Specific Considerations

For fibrinolytic therapy, enoxaparin is superior to UFH with age-adjusted dosing: 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)

For primary PCI in STEMI, UFH remains the standard due to procedural requirements for immediate anticoagulation and reversibility. 1

Comparative Efficacy and Safety Profile

LMWH demonstrates modest superiority over UFH in reducing hard endpoints. A Cochrane meta-analysis of 7 trials (11,092 patients) showed LMWH reduced MI (RR 0.83; 95% CI 0.70-0.99) and revascularization procedures (RR 0.88; 95% CI 0.82-0.95), with no difference in mortality (RR 1.0; 95% CI 0.69-1.44). 3 This translates to treating 125 patients with LMWH to prevent 1 additional MI and 50 patients to prevent 1 revascularization. 3

Bleeding risk is equivalent between LMWH and UFH for major bleeding (RR 1.00; 95% CI 0.80-1.24), though long-term LMWH increases major bleeding (OR 2.26; 95% CI 1.63-3.41). 2, 3

LMWH reduces thrombocytopenia by 64% compared to UFH (RR 0.64; 95% CI 0.44-0.94), a clinically important safety advantage. 3, 4

Fondaparinux has the lowest bleeding risk among all anticoagulants in ACS, with superior bleeding profile versus enoxaparin in OASIS-5, though this must be balanced against catheter thrombosis risk if PCI becomes necessary. 1, 5

Duration and Discontinuation

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

Never abruptly discontinue anticoagulation—premature cessation causes rebound thrombin activation with greatest reinfarction risk at 4-8 hours. 1 There is no proven benefit for prolonged outpatient LMWH beyond the acute phase in ACS. 2, 1

Practical Advantages of LMWH

LMWH offers more predictable anticoagulation without aPTT monitoring due to reduced plasma protein binding, allowing weight-based dosing without laboratory monitoring. 2, 6 The subcutaneous administration once or twice daily eliminates the need for continuous IV infusion required by UFH. 6 These practical advantages, combined with lower HIT risk, make LMWH logistically superior in most clinical settings. 2, 6