Heparin in Acute Coronary Syndrome
Anticoagulation with either unfractionated heparin (UFH) or low molecular weight heparin (LMWH) is recommended as standard therapy in acute coronary syndrome, with LMWH (specifically enoxaparin) demonstrating superior outcomes in conservative management and at least equivalent efficacy in invasive management. 1
Evidence Base for Heparin Use
Unfractionated Heparin
The evidence supporting UFH addition to aspirin in ACS is less robust than for other treatment strategies. 2 A meta-analysis of six randomized trials showed only a modest, non-significant benefit when adding UFH to aspirin (7.9% vs 10.3% death/MI rate, OR: 0.74,95% CI: 0.5–1.09, p=0.10). 2 Despite this inconclusive evidence, clinical guidelines pragmatically recommend UFH with aspirin as standard therapy. 2
Critical limitations of UFH include: 2
- Unpredictable anticoagulant response due to variable protein binding (amplified during acute phase response)
- Requires frequent aPTT monitoring and dose adjustments
- Limited effectiveness against platelet-rich and clot-bound thrombin
- Risk of heparin-induced thrombocytopenia
- Rebound phenomenon after discontinuation with loss of initial benefit 2
Low Molecular Weight Heparin Superiority
LMWH demonstrates convincing superiority over placebo (Level of Evidence: A) and offers significant advantages over UFH. 2
Key advantages of LMWH: 2
- Enhanced anti-Xa activity relative to anti-IIa activity
- Predictable anticoagulant effect without need for monitoring
- Weight-adjusted subcutaneous dosing
- Decreased sensitivity to platelet Factor 4
- Lower rates of thrombocytopenia
- More consistent antithrombin effects
Meta-analysis of four major trials (FRIC, ESSENCE, TIMI-11B, FRAXIS) showed LMWH is at least as effective as UFH overall (short-term OR: 0.86,95% CI: 0.72–1.02). 2 However, enoxaparin specifically demonstrated superiority over UFH in head-to-head comparisons for the combined endpoint of death/MI/recurrent angina. 2
Treatment Algorithm by Management Strategy
Conservative (Non-Invasive) Management
Enoxaparin is the preferred agent (Class IIa, LOE A): 2, 1
- Dosing <75 years: 30 mg IV bolus followed by 1 mg/kg subcutaneously every 12 hours 3
- Dosing ≥75 years: 0.75 mg/kg subcutaneously every 12 hours (no IV bolus) 3
- Renal adjustment (CrCl <30 mL/min): 1 mg/kg subcutaneously once daily 3
Alternative: Fondaparinux 2.5 mg subcutaneously once daily (Class IIa, LOE B) 2, 1
Registry data from 23,172 patients showed LMWH use associated with lower rates of major bleeding (1.4%) and death (1.8%) compared to UFH (1.9% and 2.5%, respectively). 4
Early Invasive Management (Planned PCI)
Either enoxaparin or UFH are equally reasonable choices (Class IIa, LOE A). 2, 1 Eleven randomized trials and seven meta-analyses document similar or improved composite outcomes with enoxaparin versus UFH in invasive management. 2, 1
UFH dosing for invasive management: 5
- Initial bolus: 60-70 U/kg (maximum 5,000 U)
- Infusion: 12-15 U/kg/h
- Target aPTT: 50-70 seconds
STEMI with Fibrinolysis
UFH is recommended with alteplase: 5
- Initial bolus: 60 U/kg (maximum 4,000 U)
- Infusion: 12 U/kg/h (maximum 1,000 U/h)
Special Populations
High Bleeding Risk
Fondaparinux (Class IIa, LOE B) or bivalirudin (Class IIa, LOE A) are preferred over UFH. 2, 1 Long-term LMWH significantly increases major bleeding risk (OR: 2.26,95% CI: 1.63–3.41, p<0.0001). 2
Renal Insufficiency
Bivalirudin or UFH are preferred (Class IIb, LOE A). 2, 1 Enoxaparin requires dose reduction to once daily when CrCl <30 mL/min. 3
Elevated Liver Enzymes
Elevated transaminases alone are NOT a contraindication to enoxaparin. 3 Exercise extreme caution only when INR ≥1.5, which indicates impaired hepatic synthetic function affecting coagulation factor production. 3 UFH may be preferred in liver failure as it allows more precise titration via aPTT monitoring. 3
Critical Pitfalls to Avoid
Never Switch Anticoagulants Mid-Treatment
Crossover between heparin types significantly increases bleeding risk (Class III, LOE C). 1 Registry data showed patients receiving crossover therapy had higher bleeding rates (2.0%) compared to consistent LMWH use (1.4%). 4
Fondaparinux Requires Special Handling at PCI
Fondaparinux increases catheter thrombosis risk when used alone and requires co-administration of UFH during PCI (Class IIb, LOE A). 2, 1 This negates its advantage as monotherapy and complicates procedural management.
Duration of Therapy
The initial benefit of heparin is lost after discontinuation (rebound phenomenon). 2 For high-risk patients with recurrent ischemia in whom revascularization is not possible, continuation of LMWH for a second week is recommended. 2 However, prolonged outpatient LMWH beyond acute treatment lacks convincing evidence of incremental benefit. 2
Monitoring Requirements
LMWH does not require aPTT monitoring, which is a major practical advantage. 2 However, baseline and serial complete blood counts are essential to detect thrombocytopenia. 3