Clinical and Pharmacological Implications of Time to Treatment with Interleukin-1 Blockade in ST-Segment Elevation Myocardial Infarction.

Abstract

Interleukin-1 (IL-1) blockade with anakinra given within 12 hours from reperfusion has been shown to reduce the inflammatory response as well as prevent heart failure (HF) events in patients with STEMI.We sought to determine whether time-to-treatment influences the efficacy of anakinra on systemic inflammation and incidence of HF events in patients with STEMI. 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. 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 time 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 treatment {greater than or equal to}271 min (235.2[131.4-603.4] vs 75.5[38.9-171.9], p<0.001) (p>0.05 for interaction). 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 Chi-square 5.985, p=0.014) as well as in patients with time from PCI to drug {greater than or equal to}271 min (2[5%] vs 7[23%], log-rank Chi-square 3.995, p=0.046) (p>0.05 for interaction). IL-1 blockade with anakinra blunts the acute systemic inflammatory response and prevents HF events independent of time-to-treatment. Significance Statement In patients with ST segment elevation presenting within 12 hours of pain onset and treated within 12 hours of reperfusion, IL-1 blockade with anakinra blunts the acute systemic inflammatory response, a surrogate of IL-1 activity, and prevents HF events independent of time-to-treatment.