Interleukin-6 Receptor Inhibition in Acute St-Segment Elevation Myocardial Infarction: A Randomised Placebo-Controlled Trial

Abstract

Background: Prompt myocardial revascularisation with percutaneous coronary intervention (PCI) reduces infarct size and improves outcomes in patients with acute ST segment elevation myocardial infarction (STEMI). However, as much as 50 % of the loss of viable myocardium may be attributed to the subsequent reperfusion injury and the associated inflammatory response. The aim of the ASSessing the effect of Anti-IL-6 treatment in Myocardial Infarction (ASSAIL-MI) trial was to evaluate the effect of interleukin-6 (IL-6) receptor inhibition on myocardial salvage in acute STEMI. Methods: The ASSAIL-MI trial was a randomised, double blind, placebo-controlled trial performed at three high-volume PCI centres in Norway. Patients admitted with STEMI within six hours of symptom onset were eligible if they had had no prior myocardial infarction. Consenting patients were randomised in a 1:1 fashion to receive a single infusion of the IL-6 receptor inhibitor tocilizumab or placebo during PCI. The primary endpoint was the myocardial salvage index as measured by cardiac magnetic resonance imaging three to seven days after randomisation. Findings: Between 16 th March 2017 and 10 th February 2020, 101 patients were randomised to tocilizumab and 98 patients were randomised to placebo. In the intention to treat analysis, the myocardial salvage index was 69 ± 19 % in patients allocated to tocilizumab and 64 ± 21 % in the placebo group (adjusted between-group difference 5.6 percentage points, 95 % confidence interval 0·0 – 11·3 percentage points, p = 0 · 04). There were 34 serious adverse events, 19 of which occurred in patients treated with tocilizumab and 15 in patients receiving placebo.Interpretation: Treatment with tocilizumab significantly improved myocardial salvage in patients presenting with acute STEMI. Funding: The South-Eastern Norway Regional Health Authority, the Central Norway Regional Health Authority, and Roche TM supported the trial. Roche™ provided the investigational medicinal products and an unrestricted grant. Trial registration number: ClinicalTrials.gov (NCT3004703). Funding Statement: The South-Eastern Norway Regional Health Authority, the Central Norway Regional Health Authority, and RocheTM supported the trial. Roche™ provided the investigational medicinal products and an unrestricted grant. Declaration of Interests: Dr Gullestad has received lecture fees from AstraZeneca, Boehringer Ingelheim, Novartis and Amgen and has been a member of local advisory board in AstraZeneca and Boehringer Ingelheim. The other authors do not have conflicts of interest pertaining to this work. Ethics Approval Statement: The trial protocol was approved by the regional ethics committee (REK Sor-Ost 2016/1223), and all participants provided written informed consent. An independent data and safety monitoring board oversaw the safety of the trial. The trial was conducted in compliance with the declaration of Helsinki and with the rules outlined in the guidelines for Good Clinical Practice.