Abstract 160: Associations Between Markers Of Inflammation And Myocardial Injury In Out-of-hospital Cardiac Arrest Patients After Treatment With Tocilizumab - A Sub Study Of The IMICA Trial

Abstract

Background: Systemic inflammation is a major component of the post-cardiac arrest syndrome. Treatment with tocilizumab, an interleukin 6 receptor antagonist, was shown in the IMICA trial to reduces systemic inflammation and markers of myocardial injury in comatose resuscitated out-of-hospital cardiac arrest (OHCA) patients. This was demonstrated by lower levels of the markers of inflammation, CRP, and leukocytes, as well as the marker of myocardial injury, Troponin T (TnT), in patients treated with tocilizumab compared to placebo. OBJECTIVE: To investigate associations between markers of inflammation and myocardial injury in the IMICA trial. Methods: At admission, 80 OHCA patients were randomized to either tocilizumab or placebo (NCT03863015). Area under the curve (AUC) between 0-72 hours was calculated for leukocyte count, CRP, and TnT. Spearman’s correlation analyses were performed after log2 transformation. Results: AUC of leukocytes correlated positively with TnT in both treatment arms (tocilizumab: r=0.4, p=0.03; placebo: r=0.4, p=0.02; see figure). Also, a positive correlation between AUC of CRP and TnT was found in patients treated with tocilizumab but not in patients receiving placebo (tocilizumab: r=0.3, p=0.03; placebo: r<0.1 p=0.86). Conclusions: These findings illustrate that in general, patients with lower levels of leukocytes also had lower levels of myocardial injury. The correlation between CRP and TnT in the tocilizumab group could possibly reflect response to treatment, or baseline activity prior to treatment. Modulation of inflammation could have cardioprotective as well as systemic effects, both of which could be possible mechanisms for the reductions in biomarkers of myocardial injury as previously reported in this trial. However, correlation does not necessarily imply causality and it is possible that other, yet uninvestigated mechanisms are responsible for the observed effects of tocilizumab.