title: Effects of the P-Selectin Antagonist Inclacumab on Myocardial Damage After Percutaneous Coronary Intervention According to Timing of Infusion: Insights From the SELECT-ACS Trial.
abstract: The Effects of the P-Selectin Antagonist Inclacumab on Myocardial Damage After Percutaneous Coronary Intervention for Non-ST-Segment Elevation Myocardial Infarction (SELECT-ACS) trial suggested beneficial effects of inclacumab, a monoclonal antibody directed against P-selectin, on periprocedural myocardial damage. This study evaluated the effect of inclacumab on myocardial damage according to varying time intervals between study drug infusion and percutaneous coronary intervention (PCI).
  
  
  
  Patients (n=544) enrolled in the SELECT-ACS trial and randomized to receive 1 infusion of placebo or inclacumab (5 or 20 mg/kg, administered between 1 and 24 hours before PCI) were divided according to the time interval between study drug infusion and PCI. The primary end point was the change in troponin I from baseline at 16 and 24 hours after PCI. In patients receiving inclacumab 20 mg/kg with a short (less than median) time interval between infusion and PCI, placebo-adjusted geometric mean percent changes in troponin I, creatine kinase-myocardial band, and peak troponin I at 24 hours were -45.6% (P=0.005), -30.7% (P=0.01), and -37.3% (P=0.02), respectively. No significant changes were observed in patients with a long (greater than median) time interval between infusion and PCI. Placebo-adjusted geometric mean percent changes in troponin I and creatine kinase-myocardial band were -43.5% (P=0.02) and -26.0% (P=0.07), respectively, when inclacumab 20 mg/kg was administered between 1 and 3 hours before PCI, whereas the drug had no effect with longer intervals.
  
  
  
  Inclacumab 20 mg/kg significantly reduces myocardial damage after PCI in patients with non-ST-segment elevation myocardial infarction, and benefits are larger when the infusion is administered <3 hours before PCI.
  
  
  
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT01327183.
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada.
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Stähli
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Gebhard
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada.
authors.forename: Valérie
authors.initials: V
authors.lastname: Duchatelle
authors.affiliation: Montreal Health Innovations Coordinating Center (MHICC), Montreal, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cournoyer
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Petroni
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Tanguay
authors.affiliation: Hoffmann-La Roche, Basel, Switzerland.
authors.forename: Stephen
authors.initials: S
authors.lastname: Robb
authors.affiliation: Hoffmann-La Roche, Basel, Switzerland.
authors.forename: Jessica
authors.initials: J
authors.lastname: Mann
authors.affiliation: Montreal Health Innovations Coordinating Center (MHICC), Montreal, Canada.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Guertin
authors.affiliation: Mayo Clinic, Rochester, MN.
authors.forename: R Scott
authors.initials: RS
authors.lastname: Wright
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: L L'Allier
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Canada jean-claude.tardif@icm-mhi.org.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D052279:Creatine Kinase, MB Form / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000517:prevention & control*; D000072658:Non-ST Elevated Myocardial Infarction / Q000628:therapy*; D019007:P-Selectin / Q000037:antagonists & inhibitors*; D062645:Percutaneous Coronary Intervention; D013997:Time Factors; D016896:Treatment Outcome; D019210:Troponin I / Q000097:blood
chemical_list: D000911:Antibodies, Monoclonal; D019007:P-Selectin; C546937:SELP protein, human; D019210:Troponin I; C000604431:inclacumab; D052279:Creatine Kinase, MB Form
keywords: acute coronary syndrome; inflammation; myocardial infarction; percutaneous coronary intervention; thrombosis