Research AppraisalRandomised Controlled Trial

Prehospital Heparin Administration in Patients With STEMI Undergoing Primary PCI: HEPARIN-STEMI Randomized Controlled Trial

CirculationFister, Misa, Noc, Marko, Radsel, Peter et al.19 May 2026DOI

Clinical Snapshot

80CEBM
Evidence: ModerateRandomised Controlled Trial

PICO Framework

P — PopulationPatients with ST-segment-elevation myocardial infarction (STEMI) with ≤6 hours symptom duration referred for primary PCI
I — Intervention70-100 IU/kg bolus of unfractionated heparin at first prehospital medical contact plus supplemental dose before PCI (adjusted to ACT ≥250 seconds)
C — ComparatorStandard unfractionated heparin administration at time of PCI only
O — OutcomesPrimary efficacy: TIMI flow grade 2-3 in infarct-related artery at initial angiography. Primary safety: BARC type 3-5 bleeding during index hospitalisation

Bottom Line

This single-centre RCT demonstrates that prehospital unfractionated heparin administration significantly improves infarct-related artery patency in STEMI patients without increasing bleeding risk. The 16% absolute improvement in TIMI flow grade 2-3 (NNT=6) represents a clinically meaningful benefit that could translate to improved myocardial salvage. While the open-label design introduces bias risk, the objective angiographic endpoint and consistent safety profile support the intervention's validity. The findings are directly applicable to Australian practice, where organised STEMI networks and paramedic capabilities would support implementation. However, confirmation through multicentre trials and assessment of long-term clinical outcomes would strengthen the evidence base before widespread adoption.

Evidence: Moderate

Key Findings

  • P Value: P<0.001

  • Effect Size: 16% absolute risk increase in arterial patency

  • Primary Outcome: TIMI flow grade 2-3 in infarct-related artery: 43% (prehospital heparin) vs 27% (control)

  • Nnt Or Sensitivity: NNT = 6 (one additional patient with patent artery for every 6 treated with prehospital heparin)

  • Confidence Interval: RR 1.59 (95% CI 1.27-1.98)

Clinical Application

Highly feasible - UFH is inexpensive, widely available, and easily administered by paramedics with appropriate training Directly applicable to Australian STEMI networks. UFH is PBS-listed and widely used. Aligns with current RACGP and Cardiac Society guidelines supporting early anticoagulation in STEMI STEMI patients within 6 hours of symptom onset in organised emergency medical systems with primary PCI capability

Abstract

BACKGROUND: Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for patients with ST-segment-elevation myocardial infarction (STEMI). We investigated the benefits and safety of pretreatment with unfractionated heparin (UFH) in patients with STEMI referred to primary PCI. METHODS: In HEPARIN-STEMI (Pretreatment With Unfractionated Heparin for ST Elevation Myocardial Infarction)-a single-center, open-label, randomized controlled trial-patients with STEMI with ≤6 hours symptom duration were assigned to receive either a 70- to 100-IE/kg bolus of UFH at first prehospital medical contact plus a supplemental dose before PCI, adjusted to activated clothing time ≥250 seconds, or to a control group receiving standard UFH at the time of PCI. The primary efficacy end point was TIMI (Thrombolysis in Myocardial Infarction) flow grade 2-3 in the infarct-related artery at initial coronary angiography. The primary safety end point was BARC (Bleeding Academic Research Consortium) type 3-5 bleeding during the index hospital stay. RESULTS: From March 2022 to February 2025, 298 patients were randomized to UFH pretreatment and 295 to the control group. The groups were comparable in age, sex, risk factors, previous cardiovascular events, and median delay from symptoms to coronary angiography (145 versus 150 minutes; P=0.814). The median time from UFH pretreatment to coronary angiography was 60 minutes (25th-75th interquartile range, 47-55 minutes). TIMI flow grade 2-3 in the infarct-related artery was documented in 43% of patients with UFH pretreatment and 27% of patients in the control group (relative risk, 1.59 [95% CI, 1.27-1.98]; P<0.001), with no significant difference in BARC type 3-5 bleeding (2.4% versus 2.0%; relative risk, 1.16 [95% CI, 0.39-3.45]; P=0.789). CONCLUSIONS: In patients with STEMI undergoing primary PCI, in a mature STEMI network, pretreatment with UFH at first prehospital medical contact was associated with an absolute 16% increase in infarct-related artery patency without an increased risk of bleeding. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05247424.

References

  1. 1.Fister, M., Noc, M., Radsel, P., Bunc, M., Franco, D., & Goslar, T. (2026). Prehospital Heparin Administration in Patients With STEMI Undergoing Primary PCI: HEPARIN-STEMI Randomized Controlled Trial. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.126.079839
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