Effects of the p-selectin antagonist inclacumab on myocardial damage according to the time interval between infusion and percutaneous coronary intervention

Purpose: P-selectin antagonism could provide anti-inflammatory, anti-thrombotic and anti-atherogenic effects. Inclacumab is a human recombinant monoclonal antibody directed against P-selectin. The SELECT-ACS trial was a multi-center, randomized, placebo-controlled phase 2 study of inclacumab. The placebo-adjusted change in troponin I (TnI) with inclacumab 20 mg/kg was -24.4% at 24 hrs (p=0.05) and -22.4% at 16 hrs (p=0.066) after percutaneous coronary intervention (PCI). Inclacumab 20 mg/kg also reduced peak TnI by 23.8% (p=0.054) and the area under the curve over 24 hrs by 33.9% (p=0.075). We aimed at determining the effects of inclacumab on myocardial damage after coronary intervention according to varying time intervals between study drug infusion and PCI. Methods: SELECT-ACS was a double-blind trial of 530 patients with non-ST elevation myocardial infarction (NSTEMI) scheduled for coronary angiography and ad hoc PCI. Patients were randomly assigned to receive one infusion of placebo, inclacumab 5 mg/kg or 20 mg/kg between 60 minutes and 24 hours before the procedure. Troponin I (TnI) and CK-MB levels were measured at baseline, and 8, 16 and 24 hours after PCI. The primary endpoint was the change from baseline in TnI to 16 and 24 hrs. There was no effect of inclacumab 5 mg/kg vs placebo. Results: The median duration between study drug infusion and PCI was 202 minutes, with no significant difference among study groups. In patients with a time interval between infusion and PCI less than the median, the placebo-adjusted geometric mean percent changes in TnI at 16 hrs and 24 hrs post-PCI in the inclacumab 20 mg/kg group were -32.5% [(-54.2, -0.6), p=0.046] and -44.6% [(-63.8, -15.4), p=0.006], whereas the changes for CK-MB were -24.4% [(-43.8, 1.7), p=0.065] and -31.0% [(-48.5, -7.5), p=0.013]. The placebo-adjusted changes in TnI and CK-MB at 24 hrs in patients with a time interval above the median were -17.7% [(-46.1, 25.9), p=0.368] and -12.6% [(-34.7, 16.9), p=0.362]. When dividing patients according to intervals of < 180 minutes, 180 to 240 minutes, and > 240 minutes, the placebo-adjusted geometric mean percent changes in TnI at 24 hrs post-PCI with inclacumab 20 mg/kg were -43.5% [(-64.9, -9.0), p=0.019], -39.4% [(-67.5, 13.1), p=0.115] and -11.3% [(-46.3, 46.4), p=0.637]; similar findings were observed for CK-MB (-27.3% [(-47.7, 0.9)], p=0.057; -29.5% [(-53.9, 7.9)], p=0.11; -11.1% [(-37.1, 25.6)], p=0.505). Conclusion: Inclacumab reduces post-PCI myocardial damage in patients with NSTEMI, and benefits appear to be the largest when the infusion occurs between 60 and 180 minutes before PCI.

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