Effects of the P-selectin antagonist inclacumab on myocardial damage after percutaneous coronary intervention for non-st-segment elevation myocardial infarction

Results of the SELECT-ACS trial

Jean Claude Tardif, Jean François Tanguay, R. Scott Wright, Valérie Duchatelle, Thibaut Petroni, Jean C. Grégoire, Reda Ibrahim, Therese M. Heinonen, Stephen Robb, Olivier F. Bertrand, Daniel Cournoyer, Dominique Johnson, Jessica Mann, Marie Claude Guertin, Philippe L. L'Allier

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Objectives: The study aimed to evaluate inclacumab for the reduction of myocardial damage during a percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation myocardial infarction. Background: P-selectin is an adhesion molecule involved in interactions between endothelial cells, platelets, and leukocytes. Inclacumab is a recombinant monoclonal antibody against P-selectin, with potential anti-inflammatory, antithrombotic, and antiatherogenic properties. Methods: Patients (N = 544) with non-ST-segment elevation myocardial infarction scheduled for coronary angiography and possible ad hoc PCI were randomized to receive 1 pre-procedural infusion of inclacumab 5 or 20 mg/kg or placebo. The primary endpoint, evaluated in patients who underwent PCI, received study medication, and had available efficacy data (n = 322), was the change in troponin I from baseline at 16 and 24 h after PCI. Results: There was no effect of inclacumab 5 mg/kg. Placebo-adjusted geometric mean percent changes in troponin I with inclacumab 20 mg/kg were -24.4% at 24 h (p = 0.05) and -22.4% at 16 h (p = 0.07). Peak troponin I was reduced by 23.8% (p = 0.05) and area under the curve over 24 h by 33.9% (p = 0.08). Creatine kinase-myocardial band yielded similar results, with changes of -17.4% at 24 h (p = 0.06) and -16.3% at 16 h (p = 0.09). The incidence of creatine kinase-myocardial band increases >3 times the upper limit of normal within 24 h was 18.3% and 8.9% in the placebo and inclacumab 20-mg/kg groups, respectively (p = 0.05). Placebo-adjusted changes in soluble P-selectin level were -9.5% (p = 0.25) and -22.0% (p < 0.01) with inclacumab 5 and 20 mg/kg. There was no significant difference in adverse events between groups. Conclusions: Inclacumab appears to reduce myocardial damage after PCI in patients with non-ST-segment elevation myocardial infarction. (A Study of RO4905417 in Patients With Non ST-Elevation Myocardial Infarction [Non-STEMI] Undergoing Percutaneous Coronary Intervention; NCT01327183)

Original languageEnglish (US)
Pages (from-to)2048-2055
Number of pages8
JournalJournal of the American College of Cardiology
Volume61
Issue number20
DOIs
StatePublished - May 21 2013

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P-Selectin
Percutaneous Coronary Intervention
Myocardial Infarction
Troponin I
Placebos
MB Form Creatine Kinase
inclacumab
Coronary Angiography
Area Under Curve
Leukocytes
Anti-Inflammatory Agents
Blood Platelets
Endothelial Cells
Monoclonal Antibodies
Non-ST Elevated Myocardial Infarction
Incidence

Keywords

  • inclacumab
  • myocardial infarction
  • P-selectin
  • percutaneous coronary intervention

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Effects of the P-selectin antagonist inclacumab on myocardial damage after percutaneous coronary intervention for non-st-segment elevation myocardial infarction : Results of the SELECT-ACS trial. / Tardif, Jean Claude; Tanguay, Jean François; Wright, R. Scott; Duchatelle, Valérie; Petroni, Thibaut; Grégoire, Jean C.; Ibrahim, Reda; Heinonen, Therese M.; Robb, Stephen; Bertrand, Olivier F.; Cournoyer, Daniel; Johnson, Dominique; Mann, Jessica; Guertin, Marie Claude; L'Allier, Philippe L.

In: Journal of the American College of Cardiology, Vol. 61, No. 20, 21.05.2013, p. 2048-2055.

Research output: Contribution to journalArticle

Tardif, JC, Tanguay, JF, Wright, RS, Duchatelle, V, Petroni, T, Grégoire, JC, Ibrahim, R, Heinonen, TM, Robb, S, Bertrand, OF, Cournoyer, D, Johnson, D, Mann, J, Guertin, MC & L'Allier, PL 2013, 'Effects of the P-selectin antagonist inclacumab on myocardial damage after percutaneous coronary intervention for non-st-segment elevation myocardial infarction: Results of the SELECT-ACS trial', Journal of the American College of Cardiology, vol. 61, no. 20, pp. 2048-2055. https://doi.org/10.1016/j.jacc.2013.03.003
Tardif, Jean Claude ; Tanguay, Jean François ; Wright, R. Scott ; Duchatelle, Valérie ; Petroni, Thibaut ; Grégoire, Jean C. ; Ibrahim, Reda ; Heinonen, Therese M. ; Robb, Stephen ; Bertrand, Olivier F. ; Cournoyer, Daniel ; Johnson, Dominique ; Mann, Jessica ; Guertin, Marie Claude ; L'Allier, Philippe L. / Effects of the P-selectin antagonist inclacumab on myocardial damage after percutaneous coronary intervention for non-st-segment elevation myocardial infarction : Results of the SELECT-ACS trial. In: Journal of the American College of Cardiology. 2013 ; Vol. 61, No. 20. pp. 2048-2055.
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abstract = "Objectives: The study aimed to evaluate inclacumab for the reduction of myocardial damage during a percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation myocardial infarction. Background: P-selectin is an adhesion molecule involved in interactions between endothelial cells, platelets, and leukocytes. Inclacumab is a recombinant monoclonal antibody against P-selectin, with potential anti-inflammatory, antithrombotic, and antiatherogenic properties. Methods: Patients (N = 544) with non-ST-segment elevation myocardial infarction scheduled for coronary angiography and possible ad hoc PCI were randomized to receive 1 pre-procedural infusion of inclacumab 5 or 20 mg/kg or placebo. The primary endpoint, evaluated in patients who underwent PCI, received study medication, and had available efficacy data (n = 322), was the change in troponin I from baseline at 16 and 24 h after PCI. Results: There was no effect of inclacumab 5 mg/kg. Placebo-adjusted geometric mean percent changes in troponin I with inclacumab 20 mg/kg were -24.4{\%} at 24 h (p = 0.05) and -22.4{\%} at 16 h (p = 0.07). Peak troponin I was reduced by 23.8{\%} (p = 0.05) and area under the curve over 24 h by 33.9{\%} (p = 0.08). Creatine kinase-myocardial band yielded similar results, with changes of -17.4{\%} at 24 h (p = 0.06) and -16.3{\%} at 16 h (p = 0.09). The incidence of creatine kinase-myocardial band increases >3 times the upper limit of normal within 24 h was 18.3{\%} and 8.9{\%} in the placebo and inclacumab 20-mg/kg groups, respectively (p = 0.05). Placebo-adjusted changes in soluble P-selectin level were -9.5{\%} (p = 0.25) and -22.0{\%} (p < 0.01) with inclacumab 5 and 20 mg/kg. There was no significant difference in adverse events between groups. Conclusions: Inclacumab appears to reduce myocardial damage after PCI in patients with non-ST-segment elevation myocardial infarction. (A Study of RO4905417 in Patients With Non ST-Elevation Myocardial Infarction [Non-STEMI] Undergoing Percutaneous Coronary Intervention; NCT01327183)",
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T1 - Effects of the P-selectin antagonist inclacumab on myocardial damage after percutaneous coronary intervention for non-st-segment elevation myocardial infarction

T2 - Results of the SELECT-ACS trial

AU - Tardif, Jean Claude

AU - Tanguay, Jean François

AU - Wright, R. Scott

AU - Duchatelle, Valérie

AU - Petroni, Thibaut

AU - Grégoire, Jean C.

AU - Ibrahim, Reda

AU - Heinonen, Therese M.

AU - Robb, Stephen

AU - Bertrand, Olivier F.

AU - Cournoyer, Daniel

AU - Johnson, Dominique

AU - Mann, Jessica

AU - Guertin, Marie Claude

AU - L'Allier, Philippe L.

PY - 2013/5/21

Y1 - 2013/5/21

N2 - Objectives: The study aimed to evaluate inclacumab for the reduction of myocardial damage during a percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation myocardial infarction. Background: P-selectin is an adhesion molecule involved in interactions between endothelial cells, platelets, and leukocytes. Inclacumab is a recombinant monoclonal antibody against P-selectin, with potential anti-inflammatory, antithrombotic, and antiatherogenic properties. Methods: Patients (N = 544) with non-ST-segment elevation myocardial infarction scheduled for coronary angiography and possible ad hoc PCI were randomized to receive 1 pre-procedural infusion of inclacumab 5 or 20 mg/kg or placebo. The primary endpoint, evaluated in patients who underwent PCI, received study medication, and had available efficacy data (n = 322), was the change in troponin I from baseline at 16 and 24 h after PCI. Results: There was no effect of inclacumab 5 mg/kg. Placebo-adjusted geometric mean percent changes in troponin I with inclacumab 20 mg/kg were -24.4% at 24 h (p = 0.05) and -22.4% at 16 h (p = 0.07). Peak troponin I was reduced by 23.8% (p = 0.05) and area under the curve over 24 h by 33.9% (p = 0.08). Creatine kinase-myocardial band yielded similar results, with changes of -17.4% at 24 h (p = 0.06) and -16.3% at 16 h (p = 0.09). The incidence of creatine kinase-myocardial band increases >3 times the upper limit of normal within 24 h was 18.3% and 8.9% in the placebo and inclacumab 20-mg/kg groups, respectively (p = 0.05). Placebo-adjusted changes in soluble P-selectin level were -9.5% (p = 0.25) and -22.0% (p < 0.01) with inclacumab 5 and 20 mg/kg. There was no significant difference in adverse events between groups. Conclusions: Inclacumab appears to reduce myocardial damage after PCI in patients with non-ST-segment elevation myocardial infarction. (A Study of RO4905417 in Patients With Non ST-Elevation Myocardial Infarction [Non-STEMI] Undergoing Percutaneous Coronary Intervention; NCT01327183)

AB - Objectives: The study aimed to evaluate inclacumab for the reduction of myocardial damage during a percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation myocardial infarction. Background: P-selectin is an adhesion molecule involved in interactions between endothelial cells, platelets, and leukocytes. Inclacumab is a recombinant monoclonal antibody against P-selectin, with potential anti-inflammatory, antithrombotic, and antiatherogenic properties. Methods: Patients (N = 544) with non-ST-segment elevation myocardial infarction scheduled for coronary angiography and possible ad hoc PCI were randomized to receive 1 pre-procedural infusion of inclacumab 5 or 20 mg/kg or placebo. The primary endpoint, evaluated in patients who underwent PCI, received study medication, and had available efficacy data (n = 322), was the change in troponin I from baseline at 16 and 24 h after PCI. Results: There was no effect of inclacumab 5 mg/kg. Placebo-adjusted geometric mean percent changes in troponin I with inclacumab 20 mg/kg were -24.4% at 24 h (p = 0.05) and -22.4% at 16 h (p = 0.07). Peak troponin I was reduced by 23.8% (p = 0.05) and area under the curve over 24 h by 33.9% (p = 0.08). Creatine kinase-myocardial band yielded similar results, with changes of -17.4% at 24 h (p = 0.06) and -16.3% at 16 h (p = 0.09). The incidence of creatine kinase-myocardial band increases >3 times the upper limit of normal within 24 h was 18.3% and 8.9% in the placebo and inclacumab 20-mg/kg groups, respectively (p = 0.05). Placebo-adjusted changes in soluble P-selectin level were -9.5% (p = 0.25) and -22.0% (p < 0.01) with inclacumab 5 and 20 mg/kg. There was no significant difference in adverse events between groups. Conclusions: Inclacumab appears to reduce myocardial damage after PCI in patients with non-ST-segment elevation myocardial infarction. (A Study of RO4905417 in Patients With Non ST-Elevation Myocardial Infarction [Non-STEMI] Undergoing Percutaneous Coronary Intervention; NCT01327183)

KW - inclacumab

KW - myocardial infarction

KW - P-selectin

KW - percutaneous coronary intervention

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