TY - JOUR
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, Scott S.
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.
N1 - Funding Information:
The study was funded by F. Hoffmann-La Roche.
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 - P-selectin
KW - inclacumab
KW - myocardial infarction
KW - percutaneous coronary intervention
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U2 - 10.1016/j.jacc.2013.03.003
DO - 10.1016/j.jacc.2013.03.003
M3 - Article
C2 - 23500230
AN - SCOPUS:84876779047
SN - 0735-1097
VL - 61
SP - 2048
EP - 2055
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 20
ER -