Unfractionated Heparin Bolus and Infusion in Unstable Angina (NSTE‑ACS)

Guideline Recommendations

Weight‑based UF heparin bolus followed by continuous infusion is a Class I, Level A recommendation for all patients with NSTE‑ACS (European Society of Cardiology guidelines) 1.
Parenteral anticoagulation should be given to every NSTE‑ACS patient at the time of diagnosis, in addition to antiplatelet therapy, regardless of ischemic or bleeding risk (Class I, Level A, ESC) 1, 2.
UF heparin remains the standard of care for NSTE‑ACS because of its favorable risk‑benefit profile (Class I, Level A, ESC) 1, 2.

Initial bolus: 60–70 IU/kg IV (maximum 4 000–5 000 IU), immediately followed by an infusion of 12–15 IU/kg/h (maximum 1 000 IU/h). This weight‑adjusted regimen is endorsed by the 2020 ESC guidelines** (Class I, Level A) 1.
During PCI: a bolus of 70–100 IU/kg is recommended; if a GP IIb/IIIa inhibitor is co‑administered, reduce the bolus to 50–70 IU/kg to limit bleeding risk** (ESC) 1.

Target activated clotting time (ACT): 250–350 seconds; if a GP IIb/IIIa inhibitor is used, aim for 200–250 seconds** (ESC) 1.

UF heparin should be stopped immediately after an uncomplicated PCI (Class I, Level A, ESC) 1, 3.

Alternative	Evidence & Recommendation	Strength / Level
Enoxaparin (LMWH)	Demonstrated superiority to UF heparin in the ESSENCE and TIMI‑11B trials; preferred unless coronary‑artery bypass grafting is planned within 24 h	Class IIa, Level A (ESC)
Fondaparinux	Recommended for medically managed patients or when PCI transfer is delayed; requires a single UF heparin bolus at the time of PCI to prevent catheter thrombosis	Class I, Level A (ESC)
Bivalirudin	May be used as an alternative to UF heparin	Class IIb, Level A (ESC)

Evidence citations: Enoxaparin superiority – 4; additional support – 5. Fondaparinux – 1. Bivalirudin – 1.

Never omit the initial UF heparin bolus because it provides immediate therapeutic anticoagulation while the infusion reaches steady state (ESC) 1.
Avoid switching between UF heparin and LMWH (crossover) as it increases bleeding without added benefit (Class III, Level B, ESC) 1, 2.
When a GP IIb/IIIa inhibitor is used, reduce the UF heparin bolus to 50–70 IU/kg (instead of 70–100 IU/kg) to minimize bleeding risk (ESC) 1.

Aspirin plus UF heparin yields a modest reduction in death or myocardial infarction compared with aspirin alone (odds ratio 0.74, 95 % CI 0.5–1.09); the pooled analysis did not achieve statistical significance (observational meta‑analysis) 6.
Heparin combined with antiplatelet agents is considered fundamental therapy (Class IA) (ESC) 5.

The American College of Cardiology recommends an initial loading dose of 60 IU/kg (maximum 4000 IU) of unfractionated heparin for patients with acute coronary syndrome, followed by an infusion of 12 IU/kg per hour (maximum 1000 IU/h) adjusted to maintain an activated partial thromboplastin time (aPTT) of 60-80 seconds 7, 8
For patients with Non-ST-Elevation ACS, the recommended loading dose is 60-70 IU/kg (maximum 4000 IU) and initial infusion is 12 IU/kg/h (maximum 1000 IU/h) 7, 8
For patients with STEMI with fibrinolytic therapy, the recommended loading dose is 60 IU/kg (maximum 4000 IU) and initial infusion is 12 IU/kg/h (maximum 1000 IU/h) 7

For patients who have received prior anticoagulant therapy, additional unfractionated heparin may be needed to achieve an activated clotting time (ACT) of 250-300 seconds 7, 8
For patients who have not received prior anticoagulant therapy, a 70-100 U/kg initial bolus may be used to achieve target ACT of 250-300 seconds 7, 8

The American College of Cardiology recommends continuing parenteral anticoagulation until revascularization (PCI or CABG) is performed 7, 8
For patients not undergoing an invasive approach, parenteral anticoagulation should be continued for the duration of hospital stay (maximum 8 days) 7

Bivalirudin is a useful alternative to unfractionated heparin in patients with STEMI undergoing PCI to reduce mortality and bleeding 7, 8
Enoxaparin is recommended for patients with Non-ST-Elevation ACS in whom an early invasive approach is not anticipated 7, 8
Fondaparinux should not be used to support PCI due to risk of catheter thrombosis 7, 8

Avoid excessive anticoagulation, as the risk of bleeding increases with higher heparin doses 9
Bleeding risk is increased with concomitant administration of fibrinolytic agents or glycoprotein IIb/IIIa inhibitors 9
Reduce dose in patients with renal impairment 8
Discontinue parenteral anticoagulation immediately after the invasive procedure unless there is a compelling reason to continue 10