An RCT of heparin in STEMI

The use of heparin in acute coronary syndrome was one of the primary gateways into my hatred of guidelines. Medical guidelines contain a lot of recommendations that aren’t exactly evidence based. When you dig into the evidence for heparin in NSTEMI, it becomes pretty clear that it shouldn’t be used, with no long term benefits but clear harms. In fact, it isn’t even clear that there is a benefit from heparin in STEMI patients, although I think it is reasonable to prescribe it. Despite rocky evidence, the guidelines use language that seems rock solid, denying any uncertainty, and so I was incredibly surprised to see an RCT of heparin in STEMI patients pop up in my feed.

The question

Does prehospital unfractionated heparin improve coronary flow at the time of PCI in STEMI patients?

The paper

Fister M, Noc M, Radsel P, Bunc M, Franco D, Goslar T; HEPARIN-STEMI Trial. Prehospital Heparin Administration in Patients With STEMI Undergoing Primary PCI: HEPARIN-STEMI Randomized Controlled Trial. Circulation. 2026 May 19;153(20):1526-1534. doi: 10.1161/CIRCULATIONAHA.126.079839. Epub 2026 Mar 30. PMID: 41910504 NCT05247424

The methods

The UFH-STEMI trial is a single center, open label RCT from Slovenia.

Patients

Adult patients with symptoms less than 6 hours, STEMI confirmed on 12 lead ECG, being transferred for PCI.

Exclusions: Pregnancy, cardiogenic shock, comatose after cardiac arrest. 

Intervention

Unfractionated heparin: 70-100 IU/kg at first medical contact, and then a subsequent dose between angiography and PCI to target an activated clotting time >250 seconds.

Comparison

No heparin in the field, but unfractionated heparin: 70-100 IU/kg between angiography and PCI. 

Outcome

The primary end point was TIMI grade 2 or 3 flow in the infarct related artery at initial angiography.

The results

They enrolled 598 patients (out of 1162 referred for primary PCI). The groups appear similar at baseline. 

Their primary outcome of TIMI flow grade 2 or 3 at initial coronary angiography was 43% in the heparin group and 27% in the control group (RR 1.59, 95% CI 1.27-1.98, p0.001). Post-procedural flow was the same in both groups. 

There was no statistical difference in bleeding (2.4% in the heparin group and 2.0% in the control group). Both groups were getting the exact same bolus of heparin, and the only thing that really changed was the timing, so the lack of harms isn’t surprising. 

There was no statistical difference in all cause mortality at 1 year (4.1% vs 2.8%, p=0.397), but the point estimate is a little higher in the heparin group. 

There are multiple clinical outcomes listed on clinicaltrials.gov (cardiogenic shock at 10 days and 30 day mortality) that aren’t mentioned anywhere in the manuscript, which is always concerning to me. They look similar when you dig into the supplementary material. 

My thoughts

I obviously think that heparin needs to be studied more in the context of ACS, but a single center unblinded trial looking at disease oriented outcomes isn’t really what we need. The whole concept of pushing therapy in the prehospital environment assumes that there is proven benefit, and I don’t think we are there yet. 

Obviously, patients don’t care about TIMI flow. This is a disease oriented outcome, which is fine to generate hypotheses, but practice really shouldn’t be changed without research showing benefits in terms of patient oriented outcomes. Of course, the patient oriented outcomes in this trial were all unchanged. (Although the trial was under-powered, the 1 year mortality was actually worse in the heparin group.) 

Unfortunately, this is an unblinded trial with a subjective outcome. There is really no reason not to blind a medication trial. This was a heparin bolus, not even an infusion. A saline placebo would have been sufficient, and very easy to arrange. The lack of a placebo really undermines the results, especially when the primary outcome is subjective and disease oriented.

I don’t really understand the cohort being studied here. They say that they studied “consecutive” PCI patients, but out of 1162 STEMI patients, they only randomized 600. There is no way that there were that many patients who were pregnant, in cardiogenic shock, or comatose post ROSC. They don’t provide any details on this screening process. Why were so many patients excluded? There seems to be a very high risk of selection bias, which is troubling in an unblinded trial. 

I know people have preached “time is muscle” for a long time, but given that TIMI flow is identical in both groups post-procedure, it seems pretty unlikely to me that giving heparin slightly earlier is actually going to result in better clinical outcomes. Of course, I remain skeptical of the value of heparin overall, so of course my priors are quite low here. I might have designed the trial with a third group who didn’t receive heparin at all (although then you would really need to focus on long term clinical outcomes, rather than TIMI flow at angiography). 

Overally, despite being a positive trial, we clearly shouldn’t be changing EMS systems to stock heparin in the prehospital environment. We need to see clinical outcomes in a properly blinded trial to warrant that kind of change. Personally, I am not convinced that heparin matters at all, but I still give it to STEMI patients when requested by cardiology (whereas I specifically do not in NSTEMI patients, as I think the data suggests net harm). 

Bottom line

This unblinded, single center trial demonstrated improved TIMI flow with prehospital heparin, but no change to real clinical outcomes. This should not change practice in any way. 

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Other FOAMed

Heparin in STEMI and PCI – does it help?

Heparin for Acute Coronary Syndrome: an evidence review

Evidence based medicine is easy

The EBM bibliography

Evidence based medicine resources

EBM deep dives

References

Fister M, Noc M, Radsel P, Bunc M, Franco D, Goslar T; HEPARIN-STEMI Trial. Prehospital Heparin Administration in Patients With STEMI Undergoing Primary PCI: HEPARIN-STEMI Randomized Controlled Trial. Circulation. 2026 May 19;153(20):1526-1534. doi: 10.1161/CIRCULATIONAHA.126.079839. Epub 2026 Mar 30. PMID: 41910504