Tocilizumab reduces cardiac injury after out-of-hospital cardiac arrest primarily in patients without acute revascularization - Results from a randomized trial, The IMICA trial

Abstract

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation (Reference no. 19-R135-A9302-22125) Lundbeck Foundation (Reference no. R186-2015-2132) BACKGROUND Patients remaining comatose after the initial resuscitation from out-of-hospital cardiac arrest (OHCA) have a high risk of morbidity and mortality as part of the ensuing post cardiac arrest syndrome (PCAS). Systemic inflammation and myocardial dysfunction are constituents of PCAS. The cytokine Interleukin-6 (IL-6) is associated with PCAS severity and poor outcome. Also, the extend of cardiac injury is a prognostic marker. We have recently shown that the IL-6 receptor antagonist tocilizumab dampens systemic inflammation and cardiac injury after cardiac arrest. PURPOSE To investigate if the reduction in cardiac injury by tocilizumab is differentiated in patients undergoing acute coronary revascularization compared to those who do not. METHODS Eighty comatose OHCA patients were randomized 1:1 in a double-blinded placebo-controlled trial to a single infusion of tocilizumab or placebo in addition to standard of care including targeted temperature management. Trial registration: Clinicaltrials.gov NCT03863015. Blood samples were sequentially drawn for biomarker analysis. Endpoints were markers of cardiac injury and inflammation: Troponin T (TnT), N-terminal pro B-type natriuretic peptide (NT-proBNP), and C-reactive protein (CRP). Continuous variables were log2 transformed and analyzed using mixed models; values shown as geometric mean with 95%-confidence limits [95%CL] after back-transformation. RESULTS Thirty-nine patients were randomized to treatment with tocilizumab and 41 to placebo. In the tocilizumab group 15 (39%) patients underwent acute revascularization (all PCI), and this was 22 (54%) for placebo. Patients not undergoing acute revascularization had a marked reduction by treatment with tocilizumab in TnT at 6h, as well as NT-proBNP at 48h (Figure). For patients treated with acute revascularization there was no significant group difference in TnT at 6h, whereas there was a marked reduction in NT-proBNP at 48h. There was a substantial reduction in CRP by treatment with tocilizumab irrespective of whether acute revascularization was performed. CONCLUSION Treatment with tocilizumab resulted in a significant reduction in myocardial injury as measured by TnT primarily in patients not undergoing acute revascularization, whereas the reduction in NT-proBNP, as well as CRP, was seen irrespective of whether acute revascularization was performed. Abstract Figure. Acute vs. NO acute revascularization