Key Points
- The UFH-STEMI Trial conducted in Slovenia demonstrated that prehospital UFH (70-100 IU/kg) at first medical contact significantly increased infarct-related artery patency at initial angiography compared with standard of care.
- The primary safety endpoint, major bleeding (BARC 3-5), did not differ between groups.
- Other variables such as ST-segment resolution and 24-hour troponin levels favored prehospital heparin, suggesting reduced myocardial injury.
Unfractionated heparin is standard anticoagulation during primary PCI for STEMI, but optimal timing of administration has remained uncertain. The UFH-STEMI trial (NCT05247424), presented at ACC.26 and simultaneously published in Circulation, tested whether a weight-adjusted UFH bolus at prehospital first medical contact would improve coronary patency compared with standard administration at the time of PCI.
UFH-STEMI was an investigator-initiated, single-center, open-label randomized trial conducted at University Medical Centre Ljubljana, Slovenia, from March 2022 to February 2025. Patients with STEMI confirmed at prehospital first medical contact and symptom duration under 6 hours were randomized 1:1 to UFH pretreatment (70-100 IU/kg IV bolus at first medical contact; n=298) or standard care (UFH after initial angiography; n=295). Patients in cardiogenic shock and cardiac arrest survivors were excluded. The primary efficacy endpoint was TIMI 2-3 flow in the infarct-related artery at initial angiography; the primary safety endpoint was BARC 3-5 bleeding.
The population was typical for contemporary STEMI: mean age 64 years, 74% male, 17% diabetic, and 52% hypertensive. Median time from symptom onset to angiography was similar between groups (145 vs. 150 minutes; p=0.814). Median time from prehospital UFH to angiography was 60 minutes. Radial access was used in 78% of cases, and PCI with stenting was performed in over 95%.
The primary efficacy endpoint occurred in 42.6% of the UFH pretreatment group versus 26.7% of controls (RR 1.59; 95% CI, 1.27-1.98; p<0.001); an absolute difference of 16 percentage points. TIMI 3 flow was present in 23.0% versus 13.7%, respectively. Critically, this benefit came without a safety tradeoff: BARC 3-5 bleeding occurred in 2.4% versus 2.0% (p=0.789). Findings were consistent in per-protocol and as-treated sensitivity analyses.
Secondary endpoints supported potential downstream benefits of improved early patency. ST-segment resolution was better with pretreatment (65% vs. 59%; p=0.047), and 24-hour troponin was significantly lower (30,357 vs. 41,795 ng/L; p=0.036), suggesting reduced myocardial injury. Final TIMI 3 flow post-PCI was similar in both groups (81% vs. 81%). The study was not powered for clinical endpoints; 30-day mortality (2.4% vs. 2.5%) and 1-year mortality (4.1% vs. 2.8%) did not differ significantly.
These findings align with the recent HELP-PCI trial from China, which also showed improved patency with early heparin, though with smaller absolute benefit (32% vs. 28% for TIMI 2-3 flow). The larger effect in UFH-STEMI may reflect shorter symptom-to-contact times in the Slovenian cohort (70 vs. 161 minutes), catching thrombus at a less organized, more heparin-sensitive stage. Patency rates matched those achieved with bivalirudin or abciximab pretreatment, but without the excess bleeding associated with those agents.
Limitations include single-center design within a mature STEMI network, exclusion of high-risk patients, and insufficient power for clinical endpoints. Prespecified subgroup analyses showed consistent treatment effects across sex, age, culprit artery, and access site, with no significant interactions.
Dr. Misa Fister, the study’s lead investigator, stated: “We found a 16% absolute difference in the patency of infarct-related arteries. The primary safety endpoint was bleeding and there was no significant difference between the groups. UFH pretreatment at first medical contact is easy, safe, and cheap.”