Abstract 13994: Time to Treatment and Efficacy of IL-1 Blockade With Anakinra in ST-Segment Elevation Myocardial Infarction

Abstract

Introduction: Interleukin-1 (IL-1) blockade with anakinra given within 12 hours from reperfusion has recently showed to reduce the inflammatory response as well as prevent heart failure (HF) events in patients with STEMI. Hypothesis: The aim of this study was to determine whether time to anakinra treatment influences the efficacy on systemic inflammation and HF events in patients with STEMI. Methods: This is a secondary analysis of the data from the three VCUART clinical trials, including adult patients with STEMI presenting within 12 hours of pain onset, enrolled within 12 hours of reperfusion and randomly assigned to anakinra or placebo for 14 days. We divided the cohort in two groups based on the median time from percutaneous coronary intervention (PCI) to investigational drug, and analyzed the effects of anakinra on the area-under-the-curve for C reactive protein (AUC-CRP) and on incidence of the composite endpoint of death or new onset HF. Results: We analyzed data from 139 patients: 84 (60%) treated with anakinra and 55 (40%) with placebo. The median time from PCI to investigational treatment was 271 [182-391] minutes. The AUC-CRP was significantly higher in patients receiving placebo versus anakinra both in those with from PCI to treatment <271 min (222.6 [103.9-325.2] vs 78.4 [44.3-131.2], p<0.001) and those with time from PCI to drug ≥271 min (235.2 [131.4-603.4] vs 75.5 [38.9-171.9, p<0.001]. Anakinra significantly reduced the combined endpoint of death or new onset HF in patients with time from PCI to treatment <271 min (5 [11%] vs 9 [36%], log-rank p value=0.014) as well as in patients with time from PCI to drug ≥271 min (2 [5%] vs 7 [23%], log-rank p value= 0.046). Conclusions: In patients with STEMI treated with anakinra within 12 hours of reperfusion, the therapeutic window of IL-1 blockade on the systemic inflammatory response and on HF events in reperfused STEMI appears to be stable for several hours.