Role of Unfractionated Heparin in Myocardial Infarction Management
Unfractionated heparin (UFH) is a cornerstone anticoagulant therapy in myocardial infarction, with specific dosing and monitoring requirements depending on the reperfusion strategy used. 1
Primary PCI Setting
Indications and Dosing
- UFH is the standard anticoagulant during primary PCI for STEMI 1
- Initial IV bolus: 70-100 U/kg (reduced to 50-60 U/kg if GPIIb/IIIa inhibitors are used) 1
- Target ACT: 250-350 seconds (200-250 seconds if GPIIb/IIIa inhibitors are used) 1
Rationale
- Prevents catheter thrombosis and acute stent thrombosis
- Reduces ischemic complications during the procedure
- The lack of randomized trials comparing heparin to placebo in PCI reflects the strong belief that anticoagulation is essential during the procedure 1
Fibrinolytic Therapy Setting
Indications and Dosing
- IV bolus: 60 U/kg (maximum 4,000 U) 1, 2
- Followed by IV infusion: 12 U/kg/hour (maximum 1,000 U/hour) 1, 2
- Target aPTT: 50-70 seconds (approximately 1.5-2.0 times control value) 1
- Duration: 24-48 hours 1
Monitoring
- First aPTT check at 3 hours after starting treatment 1
- Subsequent monitoring at 6,12, and 24 hours 1
- Dose adjustments based on aPTT results
Alternatives to UFH
Low-Molecular-Weight Heparin (LMWH)
- Enoxaparin has shown superior outcomes compared to UFH in some STEMI studies 1, 3, 4
- Benefits include more predictable anticoagulation and no need for aPTT monitoring
- In the ExTRACT-TIMI 25 trial, enoxaparin reduced death or recurrent MI compared to UFH (10.7% vs 13.8%) without increasing major bleeding 3
Direct Thrombin Inhibitors
- Bivalirudin has been studied as an alternative to UFH in primary PCI 1
- In the HORIZONS-AMI trial, bivalirudin reduced major bleeding by 40% and all-cause mortality by 1% compared to UFH plus GPIIb/IIIa inhibitors 1
- However, acute stent thrombosis occurred more frequently with bivalirudin 1
Clinical Considerations and Pitfalls
Bleeding Risk
- Major bleeding occurs in approximately 1.9% of patients receiving heparin therapy 1
- Risk increases when combined with thrombolytic agents or GPIIb/IIIa inhibitors 1
- Careful dose adjustment and monitoring are essential to minimize bleeding risk
Heparin Resistance
- More common in patients with fever, thrombosis, infections, MI, cancer, and antithrombin III deficiency 5
- Close monitoring of coagulation tests and potential dose adjustments based on anti-Factor Xa levels may be needed 5
Heparin-Induced Thrombocytopenia (HIT)
- Monitor platelet counts before and during heparin therapy 5
- Discontinue heparin if platelet count falls below 100,000/mm³ or if recurrent thrombosis develops 5
Specific Scenarios
STEMI with No Reperfusion Therapy
- UFH is still indicated to prevent thrombus propagation and recurrent ischemic events
- Weight-adjusted dosing as above with aPTT monitoring
Unstable Angina/NSTEMI
- UFH reduces the incidence of MI and recurrent angina 1, 6
- When combined with aspirin, reduces cardiovascular death and MI by approximately 30% compared to aspirin alone 1, 6
- Initial bolus of 60-70 U/kg (maximum 5,000 U) followed by 12-15 U/kg/hour infusion 1, 2
Summary of Evidence Quality
The recommendations for UFH in MI management are based on strong evidence and longstanding clinical experience. The European Society of Cardiology guidelines (2018) provide the most recent comprehensive recommendations 1, supported by earlier guidelines 1 and clinical studies. While newer anticoagulants have shown some advantages in specific settings, UFH remains a fundamental therapy in MI management due to its established efficacy, reversibility, and extensive clinical experience.