Prehospital zalunfiban improves arterial patency, 30-day outcomes in STEMI

The novel glycoprotein IIb/IIIa inhibitor zalunfiban, administered at first medical contact in patients having ST-elevation myocardial infarction (STEMI), enhances patency of the infarct-related artery upon arrival in the catheterisation laboratory, in the phase III CeleBrate trial. It also improves 30-day cardiovascular (CV) outcomes, without increasing major bleeding.

“Time is muscle, so it’s crucial to have an open infarct-related vessel when the patient arrives at the cath lab, ideally soon after prehospital diagnosis,” said lead investigator Dr Arnoud van’t Hof from the University Medical Center Maastricht, the Netherlands, at AHA 2025.

Zalunfiban is designed for prehospital use and has a lower risk of thrombocytopenia. With zalunfiban, near-complete platelet inhibition is achieved within 15 mins, and the half-life is about an hour. Platelet function typically returns to normal in about 2 hrs, allowing patients to undergo coronary artery bypass (CABG) surgery, if needed, with minimal delay and reduced bleeding risk.

Dr Christopher Granger from Duke University School of Medicine in Durham, North Carolina, US, and a CeleBrate researcher, said, “There is a clear and compelling need to enhance perfusion between initial medical contact and the cath lab. I consider this one of the most significant opportunities in all acute cardiovascular care.”

Patients have suspected STEMI

CeleBrate enrolled 2,467 patients (mean age 63 years, 79 percent male) presenting within 4 hrs of persistent ischaemic chest pain, with suspected STEMI on ECG. They were randomly assigned in a 2:1 ratio to receive either 0.11 mg/kg (n=853) or 0.13 mg/kg (n=818) of zalunfiban, which were combined into a single group for the hierarchical outcomes analysis; 796 patients received a placebo. [NEJM Evid 2025;doi:10.1056/EVIDoa2500268]

About 87 percent received zalunfiban at home or in the ambulance en route to the hospital, van’t Hof reported. Ninety-five percent of patients in both groups received aspirin, heparin, and a P2Y12 inhibitor (mainly ticagrelor) before PCI. Most procedures were performed via radial access. 

The primary endpoint was a 30-day major adverse event composite evaluated in a hierarchical fashion: all-cause death, stroke, recurrent MI, acute stent thrombosis, new-onset heart failure (HF) or rehospitalization for HF, larger infarct size, or no endpoint through 30 days. The primary safety endpoint was the occurrence of severe or life-threatening bleeding as defined by the GUSTO* criteria.

CeleBrate outcomes

Zalunfiban reduced the risk of the primary endpoint by 21 percent vs placebo (adjusted odds ratio [aOR] 0.79; p=0.028). Overall, 13.3 percent of the zalunfiban group and 9.8 percent of the placebo group experienced no CV event at 30 days (p=0.016).  “That translated into a 41 percent benefit vs placebo and a number needed to treat of 29,” said van’t Hof.

When individual components were analysed, the risk of acute stent thrombosis within 24 hrs was 82 percent lower in the zalunfiban group (p=0.007). The risk of new HF or rehospitalization for HF was 21 percent lower, although this finding was not statistically significant (p=0.17). The risk of a recurrent MI within 30 days was 65 percent higher in the zalunfiban group, but again, this was not statistically significant (p=0.23).

Importantly, patency of the infarct-related artery prior to angiography was significantly better with zalunfiban. Overall, 52 percent of patients in the zalunfiban group had TIMI Flow grade 2 or 3 in the infarct-related artery at the time of angiography vs 45 percent with placebo (p=0.002).  “This was also associated with an improvement in ST-segment resolution shortly before PCI,” reported van ’t Hof. “More patients came in with a normalised ECG.”

Severe or life-threatening bleeding rates were 1.2 percent and 0.8 percent in the zalunfiban and placebo groups, respectively (p= 0.40). Mild-to-moderate bleeding rates were significantly higher with the glycoprotein inhibitor (6.4 percent vs 1.5 percent with placebo, p<0.001).

Discussant Dr Elliott Antman from Brigham and Women’s Hospital, Boston, Massachusetts, US said the “hierarchical endpoint is challenging to interpret.”  Given the risk of bleeding, he said he would like to see future analyses break out the individual components of the hierarchical model by dose.