Key Points:
- Early pre-hospital administration of subcutaneous zalunfiban improved coronary patency and reduced composite adverse outcomes at 30 days in patients with STEMI.
- Zalunfiban reduced the likelihood of a worse 30-day multicomponent hierarchical clinical end point that included all-cause death, stroke, recurrent MI, stent thrombosis, and heart failure with no excess in severe bleeding compared with placebo.
- Findings support early platelet inhibition at first medical contact as an effective adjunct to contemporary reperfusion therapy.
The CELEBRATE trial (NCT04825743), presented at the 2025 American Heart Association Scientific Sessions and simultaneously published in NEJM Evidence, demonstrated that a single subcutaneous dose of zalunfiban, a novel glycoprotein IIb/IIIa inhibitor, administered at first medical contact improved clinical outcomes and infarct-related artery patency in patients with ST-segment elevation myocardial infarction (STEMI). This international, double-blind, placebo-controlled trial randomized 2,467 patients with suspected STEMI in a 1:1:1 ratio 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 field, in the ambulance, or upon arrival to the emergency department, prior to reperfusion therapy.
The primary efficacy endpoint, a hierarchical composite ranking of seven outcomes (all-cause death, stroke, recurrent MI, stent thrombosis, new or recurrent heart failure, larger infarct size, or no event through 30 days), was significantly improved by zalunfiban compared with placebo (adjusted OR 0.79; 95% CI, 0.65–0.98; p=0.028). Absence of any adverse clinical event occurred in 13.3% of patients receiving zalunfiban versus 9.8% with placebo, translating to an absolute risk reduction of 3.5 percentage points. Angiographic data confirmed enhanced infarct-related artery flow prior to PCI (median corrected frame count 109 [interquartile range 35 to 176] vs. 176 [interquartile range 40 to 176]; p=0.012). The incidence of severe or life-threatening bleeding was similar between groups (1.2% vs. 0.8%; p=0.40), though mild to moderate bleeding was more frequent with zalunfiban (6.4% vs. 2.5%; p<0.001).
“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, the trial’s principal investigator. “Administering potent platelet inhibition at first medical contact, before arrival to the Cath lab, may help achieve faster vessel patency and translate into improved early outcomes without compromising safety.” By enabling rapid, non-intravenous administration of potent platelet inhibition, CELEBRATE introduces a potential paradigm shift in prehospital STEMI care. The results suggest that early glycoprotein IIb/IIIa blockade using subcutaneous zalunfiban could enhance the effectiveness of current reperfusion strategies, paving the way for broader adoption of frontline pharmacologic reperfusion adjuncts in acute coronary care.