Zalunfiban at First Medical Contact for ST-Elevation Myocardial Infarction

A W J Van't Hof; C M Gibson; S A O F Rikken; J L Januzzi; C B Granger; A van Beurden; S Rasoul; L Ruiters; J Vainer; A Verburg; F Arslan; J W Jukema; M Durieux; J Polad; R van Vliet; B J L van den Branden; M Magro; W Remkes; J Beelen; R Hermanides; R Tolsma; M Gosselink; D Vinereanu; V Chioncel; T P van de Hoef; R Boomars; K E Arkenbout; G K van Houwelingen; G Hengstman; H van de Wetering; R Pisters; P Kala; B Merkely; P Ecollan; F Lapostolle; R P Giugliano; R C Welsh; M Levy; A Arias-Mendoza; N Baron; D Cociorva; J Wittes; E F Unger; B S Coller; J M Ten Berg; G Montalescot

doi:10.1056/EVIDoa2500268

Zalunfiban at First Medical Contact for ST-Elevation Myocardial Infarction

A W J Van't Hof
, C M Gibson
, S A O F Rikken
, J L Januzzi
, C B Granger
, A van Beurden
, S Rasoul
, L Ruiters
, J Vainer
, A Verburg
, F Arslan
, J W Jukema
, M Durieux
, J Polad
, R van Vliet
, B J L van den Branden
, M Magro
, W Remkes
, J Beelen
, R Hermanides

R Tolsma, M Gosselink, D Vinereanu, V Chioncel, T P van de Hoef, R Boomars, K E Arkenbout, G K van Houwelingen, G Hengstman, H van de Wetering, R Pisters, P Kala, B Merkely, P Ecollan, F Lapostolle, R P Giugliano, R C Welsh, M Levy, A Arias-Mendoza, N Baron, D Cociorva, J Wittes, E F Unger, B S Coller, J M Ten Berg, G Montalescot

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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).

Original language	English
Article number	EVIDoa2500268
Journal	NEJM evidence
Volume	5
Issue number	1
Early online date	10 Nov 2025
DOIs	https://doi.org/10.1056/EVIDoa2500268
Publication status	Published - 2026

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EVIDoa2500268
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Van't Hof, A. W. J., Gibson, C. M., Rikken, S. A. O. F., Januzzi, J. L., Granger, C. B., van Beurden, A., Rasoul, S., Ruiters, L., Vainer, J., Verburg, A., Arslan, F., Jukema, J. W., Durieux, M., Polad, J., van Vliet, R., van den Branden, B. J. L., Magro, M., Remkes, W., Beelen, J., ... Montalescot, G. (2026). Zalunfiban at First Medical Contact for ST-Elevation Myocardial Infarction. NEJM evidence, 5(1), Article EVIDoa2500268. https://doi.org/10.1056/EVIDoa2500268

@article{633b3459cca145f1a1e7fa3e38629dad,

title = "Zalunfiban at First Medical Contact for ST-Elevation Myocardial Infarction",

abstract = "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).",

author = "\{Van't Hof\}, \{A W J\} and Gibson, \{C M\} and Rikken, \{S A O F\} and Januzzi, \{J L\} and Granger, \{C B\} and \{van Beurden\}, A and S Rasoul and L Ruiters and J Vainer and A Verburg and F Arslan and Jukema, \{J W\} and M Durieux and J Polad and \{van Vliet\}, R and \{van den Branden\}, \{B J L\} and M Magro and W Remkes and J Beelen and R Hermanides and R Tolsma and M Gosselink and D Vinereanu and V Chioncel and \{van de Hoef\}, \{T P\} and R Boomars and Arkenbout, \{K E\} and \{van Houwelingen\}, \{G K\} and G Hengstman and \{van de Wetering\}, H and R Pisters and P Kala and B Merkely and P Ecollan and F Lapostolle and Giugliano, \{R P\} and Welsh, \{R C\} and M Levy and A Arias-Mendoza and N Baron and D Cociorva and J Wittes and Unger, \{E F\} and Coller, \{B S\} and \{Ten Berg\}, \{J M\} and G Montalescot",

year = "2026",

doi = "10.1056/EVIDoa2500268",

language = "English",

volume = "5",

journal = "NEJM evidence",

issn = "2766-5526",

publisher = "Massachussetts Medical Society",

number = "1",

}

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 2026, 'Zalunfiban at First Medical Contact for ST-Elevation Myocardial Infarction', NEJM evidence, vol. 5, no. 1, EVIDoa2500268. https://doi.org/10.1056/EVIDoa2500268

TY - JOUR

T1 - Zalunfiban at First Medical Contact for ST-Elevation Myocardial Infarction

AU - Van't Hof, A W J

AU - Gibson, C M

AU - Rikken, S A O F

AU - Januzzi, J L

AU - Granger, C B

AU - van Beurden, A

AU - Rasoul, S

AU - Ruiters, L

AU - Vainer, J

AU - Verburg, A

AU - Arslan, F

AU - Jukema, J W

AU - Durieux, M

AU - Polad, J

AU - van Vliet, R

AU - van den Branden, B J L

AU - Magro, M

AU - Remkes, W

AU - Beelen, J

AU - Hermanides, R

AU - Tolsma, R

AU - Gosselink, M

AU - Vinereanu, D

AU - Chioncel, V

AU - van de Hoef, T P

AU - Boomars, R

AU - Arkenbout, K E

AU - van Houwelingen, G K

AU - Hengstman, G

AU - van de Wetering, H

AU - Pisters, R

AU - Kala, P

AU - Merkely, B

AU - Ecollan, P

AU - Lapostolle, F

AU - Giugliano, R P

AU - Welsh, R C

AU - Levy, M

AU - Arias-Mendoza, A

AU - Baron, N

AU - Cociorva, D

AU - Wittes, J

AU - Unger, E F

AU - Coller, B S

AU - Ten Berg, J M

AU - Montalescot, G

PY - 2026

Y1 - 2026

N2 - 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).

AB - 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).

U2 - 10.1056/EVIDoa2500268

DO - 10.1056/EVIDoa2500268

M3 - Article

C2 - 41211981

SN - 2766-5526

VL - 5

JO - NEJM evidence

JF - NEJM evidence

IS - 1

M1 - EVIDoa2500268

ER -

Zalunfiban at First Medical Contact for ST-Elevation Myocardial Infarction

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