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

J Am Heart Assoc. 2016 Nov 16;5(11):e004255. doi: 10.1161/JAHA.116.004255.

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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Creatine Kinase, MB Form / blood
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Reperfusion Injury / blood
  • Myocardial Reperfusion Injury / prevention & control*
  • Non-ST Elevated Myocardial Infarction / therapy*
  • P-Selectin / antagonists & inhibitors*
  • Percutaneous Coronary Intervention*
  • Time Factors
  • Treatment Outcome
  • Troponin I / blood

Substances

  • Antibodies, Monoclonal
  • P-Selectin
  • SELP protein, human
  • Troponin I
  • inclacumab
  • Creatine Kinase, MB Form

Associated data

  • ClinicalTrials.gov/NCT01327183