In a patient with ST‑segment‑elevation myocardial infarction undergoing primary percutaneous coronary intervention, what is the preferred anticoagulant and its dosing and infusion protocol, including alternatives and adjustments for renal impairment or high bleeding risk?

Anticoagulation in STEMI During Primary PCI

Preferred Anticoagulant and Dosing

Unfractionated heparin (UFH) remains the routine recommended anticoagulant for primary PCI in STEMI, administered as a weight-adjusted intravenous bolus of 70–100 U/kg (or 50–70 U/kg if glycoprotein IIb/IIIa inhibitors are planned), targeting an activated clotting time (ACT) of 250–350 seconds (or 200–250 seconds with GP IIb/IIIa inhibitors). 1

UFH Dosing Protocol

• Without planned GP IIb/IIIa inhibitors: 70–100 U/kg IV bolus, target ACT 250–300 seconds (HemoTec) or 300–350 seconds (Hemochron device) 1
• With planned GP IIb/IIIa inhibitors: 50–70 U/kg IV bolus, target ACT 200–250 seconds 1
• Infusion: Weight-adjusted continuous infusion with first aPTT control after 3 hours 1
• Additional boluses: Administer as needed during the procedure to maintain therapeutic ACT 1

Alternative Anticoagulants

Enoxaparin

Enoxaparin should be considered as an alternative to UFH in STEMI patients undergoing primary PCI, based on evidence showing superiority in reducing death and major bleeding compared to UFH. 1

• Dosing: IV bolus followed by subcutaneous administration 1, 2
• If prior subcutaneous dose given:
  • If last dose was ≥8–12 hours earlier: give 0.3 mg/kg IV 1
  • If last dose was within 8 hours: no additional dose needed 1
• Evidence: Meta-analysis of 23 PCI trials (30,966 patients) showed enoxaparin reduced death compared to UFH, particularly in primary PCI, with reduced major bleeding 1

Bivalirudin

Bivalirudin should be considered as an alternative anticoagulant, particularly in patients at high risk of bleeding, though it carries increased risk of acute stent thrombosis. 1

• Dosing: 0.75 mg/kg IV bolus, followed by 1.75 mg/kg/h infusion 1, 3
• Additional bolus: 0.3 mg/kg may be given if needed (assess ACT 5 minutes after initial bolus) 3
• Duration: Consider extending infusion for up to 4 hours post-procedure in STEMI patients 3
• Advantages: 40% reduction in major bleeding versus UFH plus GP IIb/IIIa inhibitors, with lower 30-day mortality 1
• Disadvantages: Higher rate of acute stent thrombosis (particularly within first 24 hours) 1
• Switching strategy: Patients who received UFH pre-hospital can be switched to bivalirudin before PCI with reduced bleeding and improved survival 4

Fondaparinux

Fondaparinux is contraindicated as the sole anticoagulant for primary PCI due to increased catheter thrombosis and lack of efficacy benefit. 1

Renal Impairment Adjustments

UFH

• No dose adjustment required for any degree of renal impairment; dose by weight and monitor ACT 1

Bivalirudin

• CrCl <30 mL/min: Reduce infusion to 1 mg/kg/h (no change to bolus dose) 3
• Hemodialysis: Reduce infusion to 0.25 mg/kg/h (no change to bolus dose) 3

Enoxaparin

• Use with caution in severe renal impairment; consider UFH or bivalirudin as alternatives 1

High Bleeding Risk Patients

In patients at high risk of bleeding, bivalirudin is preferred over UFH with GP IIb/IIIa inhibitors (Class IIa recommendation). 1

• Bivalirudin reduces major bleeding by approximately 3.75% compared to UFH, with much of this benefit attributable to reduced GP IIb/IIIa inhibitor use 5
• The bleeding reduction is most pronounced with femoral access; minimal benefit seen with radial access 5
• Consider 81 mg aspirin maintenance dose rather than higher doses to further reduce bleeding risk 1

Critical Infusion Protocol Details

UFH Administration

1. Calculate weight-based bolus dose (70–100 U/kg or 50–70 U/kg with GP IIb/IIIa) 1
2. Administer IV bolus at start of procedure 1
3. Check ACT 5–10 minutes after bolus 1
4. Give additional boluses as needed to maintain target ACT throughout procedure 1
5. Continue weight-adjusted infusion post-procedure with aPTT monitoring 1

Bivalirudin Administration

1. Administer 0.75 mg/kg IV bolus 1, 3
2. Start 1.75 mg/kg/h infusion immediately 1, 3
3. Check ACT at 5 minutes; give 0.3 mg/kg additional bolus if needed 3
4. Continue infusion for duration of procedure 3
5. For STEMI specifically: Consider extending infusion at 1.75 mg/kg/h for up to 4 hours post-procedure 3
6. Terminate infusion at end of procedure (or after 4-hour extension in STEMI) 1, 3

Common Pitfalls and Caveats

• Do not use fondaparinux for primary PCI—it is associated with catheter thrombosis 1
• Bivalirudin increases acute stent thrombosis risk: This occurs primarily in the first 24 hours and may be mitigated by prior UFH use and adequate P2Y12 inhibitor loading (600 mg clopidogrel preferred over 300 mg) 1
• GP IIb/IIIa inhibitor use drives bleeding differences: Much of bivalirudin's bleeding benefit versus UFH is explained by lower GP IIb/IIIa use (26.5% vs 74.7%); when GP IIb/IIIa use is equalized, bleeding differences narrow substantially 5
• ACT monitoring is essential with UFH: Failure to achieve therapeutic ACT increases thrombotic complications 1
• Heparin-induced thrombocytopenia: Bivalirudin is the recommended anticoagulant in patients with known or suspected HIT 1, 3
• Avoid coronary brachytherapy with bivalirudin: Increased thrombus formation, including fatal outcomes, has been reported 3