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

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.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01327183.

Keywords: acute coronary syndrome; inflammation; myocardial infarction; percutaneous coronary intervention; thrombosis.

© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

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Source: PubMed

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