title: 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.
abstract: OBJECTIVE
  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).
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada. jean-claude.tardif@icm-mhi.org
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Tanguay
authors.forename: Scott R
authors.initials: SR
authors.lastname: Wright
authors.forename: Valérie
authors.initials: V
authors.lastname: Duchatelle
authors.forename: Thibaut
authors.initials: T
authors.lastname: Petroni
authors.forename: Jean C
authors.initials: JC
authors.lastname: Grégoire
authors.forename: Reda
authors.initials: R
authors.lastname: Ibrahim
authors.forename: Therese M
authors.initials: TM
authors.lastname: Heinonen
authors.forename: Stephen
authors.initials: S
authors.lastname: Robb
authors.forename: Olivier F
authors.initials: OF
authors.lastname: Bertrand
authors.forename: Daniel
authors.initials: D
authors.lastname: Cournoyer
authors.forename: Dominique
authors.initials: D
authors.lastname: Johnson
authors.forename: Jessica
authors.initials: J
authors.lastname: Mann
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Guertin
authors.forename: Philippe L
authors.initials: PL
authors.lastname: L'Allier
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D019007:P-Selectin / Q000037:antagonists & inhibitors*; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects*; D011292:Premedication; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome; D019210:Troponin I / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D019007:P-Selectin; D011994:Recombinant Proteins; D019210:Troponin I; C000604431:inclacumab; D052279:Creatine Kinase, MB Form