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

• Published in: Journal of the American College of Cardiology 2013-05, Vol.61 (20), p.2048-2055
• Main Authors: TARDIF, Jean-Claude, TANGUAY, Jean-François, COURNOYER, Daniel, JOHNSON, Dominique, MANN, Jessica, GUERTIN, Marie-Claude, L'ALLIER, Philippe L, WRIGHT, Scott S, DUCHATELLE, Valérie, PETRONI, Thibaut, GREGOIRE, Jean C, IBRAHIM, Reda, HEINONEN, Therese M, ROBB, Stephen, BERTRAND, Olivier F
• Format: Article
• Language: English
• Subjects: Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - therapeutic use; Biological and medical sciences; Cardiology. Vascular system; Coronary heart disease; Creatine Kinase, MB Form - metabolism; Diseases of the cardiovascular system; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heart; Humans; Immunologic Factors - administration & dosage; Immunologic Factors - therapeutic use; Male; Medical sciences; Middle Aged; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardial Infarction - therapy; Myocarditis. Cardiomyopathies; P-Selectin - antagonists & inhibitors; Percutaneous Coronary Intervention - adverse effects; Premedication; Prospective Studies; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Recombinant Proteins - therapeutic use; Treatment Outcome; Troponin I - metabolism
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2013.03.003

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. 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. 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. 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. 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).