Impact of tocilizumab on endothelial function following out-of-hospital cardiac arrest: a substudy of the IMICA randomized controlled trial

Abstract Aims Biomarkers of endothelial activation and damage are elevated after out-of-hospital cardiac arrest (OHCA). Elevated plasma concentrations of syndecan-1, soluble thrombomodulin (sTM), and platelet endothelial cell adhesion molecule 1 (PECAM-1) reflect glycocalyx degradation, endothelial cell injury, and endothelial junction disruption, respectively. Interleukin 6 (IL-6) plays an important role in the inflammatory mechanisms that cause endothelial damage, and inhibiting IL-6 with tocilizumab may attenuate endothelial damage. The present study examines the effect of tocilizumab on endothelial biomarkers and their prognostic value in comatose resuscitated OHCA patients. Methods and results The ‘IL-6 Inhibition for Modulating Inflammation after Cardiac Arrest’ (IMICA) trial included 80 comatose OHCA patients who were randomized to receive tocilizumab (8 mg/kg) or placebo. Blood samples were drawn sequentially at hospital admission (0 h) and after 24, 48, and 72 h for biomarker measurements. Syndecan-1 concentrations declined over time in both groups; however, the reduction was significantly less in the tocilizumab group (all P < 0.003). No significant between-group differences were observed for sTM or PECAM-1. In prognostic analyses, baseline PECAM-1 had an AUROC of 0.71 (95% CI 0.59–0.83) for prediction of 30-day mortality. Syndecan-1 and sTM had no predictive value (AUROC 0.61 and 0.53, respectively). Conclusion Plasma syndecan-1 decline was less pronounced in comatose OHCA patients treated with tocilizumab, without affecting sTM or PECAM-1. This contrasts with previous IMICA findings of reduced systemic inflammation, vasopressor use, and myocardial injury, suggesting a complex relationship between inflammation and endothelial injury. Finally, PECAM-1 levels already at hospital admission had a moderate predictive value for mortality. Clinical trial registration The trial is registered at clinicaltrials.gov (NCT03863015).