NEJM evidence, 10 2 2025, Pages EVIDoa2500268 Zalunfiban at First Medical Contact for ST-Elevation Myocardial Infarction. Van't Hof AWJ, Gibson CM, Rikken SAOF, Januzzi JL, Granger CB, van Beurden A, Rasoul S, Ruiters L, Vainer J, Verburg A, Arslan F, Jukema JW, Durieux M, Polad J, van Vliet R, van den Branden BJL, Magro M, Remkes W, Beelen J, Hermanides R, Tolsma R, Gosselink M, Vinereanu D, Chioncel V, van de Hoef TP, Boomars R, Arkenbout KE, van Houwelingen GK, Hengstman G, van de Wetering H, Pisters R, Kala P, Merkely B, Ecollan P, Lapostolle F, Giugliano RP, Welsh RC, Levy M, Arias-Mendoza A, Baron N, Cociorva D, Wittes J, Unger EF, Coller BS, Ten Berg JM, Montalescot G
Background
Zalunfiban is a glycoprotein IIb/IIIa (integrin αIIbβ3) inhibitor designed for subcutaneous administration on first medical contact with patients with suspected ST-segment elevation myocardial infarction (STEMI).
Methods
An international, double-blind, placebo-controlled trial randomly assigned patients with STEMI in a 1:1:1 ratio to receive a single subcutaneous injection of zalunfiban (0.11 mg/kg or 0.13 mg/kg) or placebo. The primary efficacy end point was a hierarchical proportional odds model ranking seven end points from worst to best: all-cause death, stroke, recurrent myocardial infarction, acute stent thrombosis, new-onset or rehospitalization for heart failure, larger infarct size, or no end point through 30 days. The primary safety end point was the occurrence of severe or life-threatening bleeding as per the global use of strategies to open occluded coronary arteries (GUSTO) criteria.
Results
The trial randomly assigned 2467 patients (853 to zalunfiban 0.11 mg/kg, 818 to zalunfiban 0.13 mg/kg, and 796 to placebo). The primary efficacy end point was significantly improved by zalunfiban (adjusted odds ratio 0.79; 95% confidence interval, 0.65 to 0.98; P=0.028). GUSTO severe bleeding was similar between those who received zalunfiban versus placebo (1.2% vs. 0.8%; P=0.40), but GUSTO mild to moderate bleeding was increased (6.4% vs. 2.5%; P<0.001). Angiography showed faster coronary blood flow with zalunfiban versus placebo (corrected frame count of the infarct-related artery 109 [interquartile range 35 to 176] vs. 176 [interquartile range 40 to 176]; P=0.012).
Conclusions
In patients with STEMI, zalunfiban administered at first medical contact significantly improved preintervention infarct-related patency and reduced the likelihood of a worse 30-day multicomponent hierarchical clinical end point. Zalunfiban was not associated with increased severe or life-threatening bleeding but was associated with increased mild to moderate bleeding. (Funded by CeleCor Therapeutics; CELEBRATE ClinicalTrials.gov number, NCT04825743).
