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, Scott S. 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

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94 Scopus citations

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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Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Tardif, J. C., Tanguay, J. F., Wright, S. S., Duchatelle, V., Petroni, T., Grégoire, J. C., Ibrahim, R., Heinonen, T. M., Robb, S., Bertrand, O. F., Cournoyer, D., Johnson, D., Mann, J., Guertin, M. C., & L'Allier, P. L. (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, 61(20), 2048-2055. https://doi.org/10.1016/j.jacc.2013.03.003