Interleukin-1 blockade in patients with ST-segment elevation myocardial infarction with and without history of coronary artery disease

Background Patients with a history of coronary artery disease (CAD) commonly present with a more advanced atherosclerotic disease burden and a higher prevalence of microvascular dysfunction compared to those without a history of CAD, which may predispose to greater to systemic inflammation and myocardial injury.Interleukin-1 may play a role in the acute inflammatory response during ST-segment elevation myocardial inflammation infarction (STEMI) and in is associated with higher risk of systolic dysfunction and heart failure (HF). The aim of the present study is to evaluate the impact of anakinra, an IL-1 blocker, on systemic inflammation and heart failure in myocardial infarction with ST-segment elevation (STEMI) patients, stratified with and without prior history of CAD. Methods We pooled data from 3 randomized phase 2 clinical trials, included 139 patients with STEMI, Patients were stratified by history of CAD based on the following criteria: prior non-ST-segment-elevation myocardial infarction, prior finding of obstructive CAD at invasive or non-invasive angiography, prior revascularization with percutaneous coronary intervention or coronary artery bypass graft surgery. The area-under-the-curve for C reactive protein (CRP-AUC) at 14 days post-STEMI was used as a measure for systemic inflammation. Event-free survival from a composite outcome of new-onset heart failure, HF hospitalization, or death was analyzed and compared for patients with and without history of CAD using Cox regression analysis. Results Treatment with anakinra was associated with significantly lower AUC-CRP levels compared with placebo, no difference based on a prior history of CAD (P for interaction=0.27).Fewer patients treated with anakinra experienced new onset heart failure or death than placebo, and there were no significant interactions between groups stratified by history of CAD and treatment allocation to anakinra or placebo for the composite outcome of all-cause death, new-onset HF or HF hospitalization (P for interaction=0.48, Figure 1). As a sensitivity analysis, we repeated the assessments comparing those with treatment with aspirin or statins prior to admission for STEMI, as surrogates for history of CAD and we found no significant interaction between treatment and effect and aspirin or statin use (P for interaction 0.61 and 0.14, for aspirin and statins use, respectively). Conclusions Patients with a history of CAD presenting with STEMI have a similar systemic inflammatory response, measured as the area-under-the-curve for CRP than those without prior history of CAD, and they also experienced a similar reduction in CRP levels with anakinra. No heterogeneity of treatment effect for anakinra on death or heart failure events was found comparing those with and without history of CAD.