A single subcutaneous injection of zalunfiban administered on first medical contact with patients with suspected STEMI was associated with improved patency of the infarct-related artery at index angiography and a significantly lower chance of all-cause death, stroke, recurrent myocardial infarction (MI), stent thrombosis, heart failure and larger MI at 30 days, based on findings from CELEBRATE presented at AHA 2025 and simultaneously published in NEJM Evidence.

Researchers randomly assigned 2,467 patients with STEMI to receive zalunfiban 0.11 mg/kg (n=853), zalunfiban 0.13 mg/kg (n=818) or placebo (n=796) at first medical contact, either in the patient's home, the ambulance or the emergency department. The primary efficacy endpoint was a hierarchical proportional odds model ranking seven endpoints from worst to best: all-cause death, stroke, recurrent MI, acute stent thrombosis, new-onset or rehospitalization for heart failure, larger infarct size, or no endpoint through 30 days. The primary safety endpoint was the occurrence of major bleeding.

Overall, the primary efficacy endpoint was significantly improved by zalunfiban (adjusted odds ratio 0.79; 95% confidence interval, 0.65 to 0.98; p=0.028), according to the study investigators. The absence of any major adverse clinical endpoint occurred in 13.3% of those receiving zalunfiban compared with 9.8% of those receiving placebo, an absolute risk reduction of 3.5 percentage points. The occurrence of severe bleeding was similar between the two groups, but increased mild to moderate bleeding was observed in the zalunfiban group.

"These data speak to the efficacy and safety profile of early subcutaneous platelet inhibition as an adjunct to state-of-the-art reperfusion therapy in STEMI," said Arnoud Willem van 't Hof, MD, PhD, and colleagues.

In a related editorial comment, Marc-André d'Entremont, MD, MPH, and Sanjit S. Jolly, MD, MSc, write that the "CELEBRATE trial brings back a treatment option that has been set aside for over a decade by transforming a hospital-based infusion into a field-ready subcutaneous injection with ideal pharmacokinetic properties for pretreatment." They add that "if subsequent randomized controlled trials confirm its effectiveness for hard clinical outcomes, similar agents could reestablish GPIIb/IIIa inhibition as an effective upstream therapy in patients with STEMI, with balanced and careful consideration for ischemic benefits and bleeding risks."

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Invasive Cardiovascular Angiography and Intervention, Anticoagulation Management and ACS, Interventions and ACS, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: AHA Annual Scientific Sessions, AHA25, Acute Coronary Syndrome, Angiography, Anticoagulants