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

Barbara E. Stähli, Catherine Gebhard, Valërie Duchatelle, Daniel Cournoyer, Thibaut Petroni, Jean Francois Tanguay, Stephen Robb, Jessica Mann, Marie Claude Guertin, R. Scott Wright, Philippe L. L'Allier, Jean Claude Tardif

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background--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). Methods and Results--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. Conclusions--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.

Original languageEnglish (US)
Article numbere004255
JournalJournal of the American Heart Association
Volume5
Issue number11
DOIs
StatePublished - Nov 1 2016

Fingerprint

P-Selectin
Percutaneous Coronary Intervention
Troponin I
MB Form Creatine Kinase
Placebos
inclacumab
Pharmaceutical Preparations
Monoclonal Antibodies

Keywords

  • Acute coronary syndrome
  • Inflammation
  • Myocardial infarction
  • Percutaneous coronary intervention
  • Thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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. / Stähli, Barbara E.; Gebhard, Catherine; Duchatelle, Valërie; Cournoyer, Daniel; Petroni, Thibaut; Tanguay, Jean Francois; Robb, Stephen; Mann, Jessica; Guertin, Marie Claude; Wright, R. Scott; L'Allier, Philippe L.; Tardif, Jean Claude.

In: Journal of the American Heart Association, Vol. 5, No. 11, e004255, 01.11.2016.

Research output: Contribution to journalArticle

Stähli, Barbara E. ; Gebhard, Catherine ; Duchatelle, Valërie ; Cournoyer, Daniel ; Petroni, Thibaut ; Tanguay, Jean Francois ; Robb, Stephen ; Mann, Jessica ; Guertin, Marie Claude ; Wright, R. Scott ; L'Allier, Philippe L. ; Tardif, Jean Claude. / 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. In: Journal of the American Heart Association. 2016 ; Vol. 5, No. 11.
@article{09b5951d10024228ac15cc70adefe4f9,
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 = "Background--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). Methods and Results--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. Conclusions--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.",
keywords = "Acute coronary syndrome, Inflammation, Myocardial infarction, Percutaneous coronary intervention, Thrombosis",
author = "St{\"a}hli, {Barbara E.} and Catherine Gebhard and Val{\"e}rie Duchatelle and Daniel Cournoyer and Thibaut Petroni and Tanguay, {Jean Francois} and Stephen Robb and Jessica Mann and Guertin, {Marie Claude} and Wright, {R. Scott} and L'Allier, {Philippe L.} and Tardif, {Jean Claude}",
year = "2016",
month = "11",
day = "1",
doi = "10.1161/JAHA.116.004255",
language = "English (US)",
volume = "5",
journal = "Journal of the American Heart Association",
issn = "2047-9980",
publisher = "Wiley-Blackwell",
number = "11",

}

TY - JOUR

T1 - Effects of the P-Selectin Antagonist Inclacumab on Myocardial Damage After Percutaneous Coronary Intervention According to Timing of Infusion

T2 - Insights from the SELECT-ACS Trial

AU - Stähli, Barbara E.

AU - Gebhard, Catherine

AU - Duchatelle, Valërie

AU - Cournoyer, Daniel

AU - Petroni, Thibaut

AU - Tanguay, Jean Francois

AU - Robb, Stephen

AU - Mann, Jessica

AU - Guertin, Marie Claude

AU - Wright, R. Scott

AU - L'Allier, Philippe L.

AU - Tardif, Jean Claude

PY - 2016/11/1

Y1 - 2016/11/1

N2 - Background--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). Methods and Results--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. Conclusions--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.

AB - Background--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). Methods and Results--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. Conclusions--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.

KW - Acute coronary syndrome

KW - Inflammation

KW - Myocardial infarction

KW - Percutaneous coronary intervention

KW - Thrombosis

UR - http://www.scopus.com/inward/record.url?scp=85025175567&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85025175567&partnerID=8YFLogxK

U2 - 10.1161/JAHA.116.004255

DO - 10.1161/JAHA.116.004255

M3 - Article

C2 - 27852589

AN - SCOPUS:85025175567

VL - 5

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

SN - 2047-9980

IS - 11

M1 - e004255

ER -