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Background - Prompt myocardial revascularization with percutaneous coronary intervention (PCI) reduces infarct size and improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI). However, as much as 50% of the loss of viable myocardium may be attributed to the reperfusion injury and the associated inflammatory response. Objectives - This study sought to evaluate the effect of the interleukin-6 receptor inhibitor tocilizumab on myocardial salvage in acute STEMI. Methods - The ASSAIL-MI trial was a randomized, double-blind, placebo-controlled trial conducted at 3 high-volume PCI centers in Norway. Patients admitted with STEMI within 6 h of symptom onset were eligible. Consenting patients were randomized in a 1:1 fashion to promptly receive a single infusion of 280 mg tocilizumab or placebo. The primary endpoint was the myocardial salvage index as measured by magnetic resonance imaging after 3 to 7 days. Results - We randomized 101 patients to tocilizumab and 98 patients to placebo. The myocardial salvage index was larger in the tocilizumab group than in the placebo group (adjusted between-group difference 5.6 [95% confidence interval: 0.2 to 11.3] percentage points, p = 0.04). Microvascular obstruction was less extensive in the tocilizumab arm, but there was no significant difference in the final infarct size between the tocilizumab arm and the placebo arm (7.2% vs. 9.1% of myocardial volume, p = 0.08). Adverse events were evenly distributed across the treatment groups. Conclusions - Tocilizumab increased myocardial salvage in patients with acute STEMI. (ASSessing the effect of Anti-IL-6 treatment in Myocardial Infarction [ASSAIL-MI]; NCT03004703)

Background We recently showed that interleukin (IL)-6 inhibition by tocilizumab improves myocardial salvage in ST-elevation myocardial infarction (STEMI). However, the mechanisms for this effect are not clear. Methods In this exploratory sub-study of the ASSAIL-MI trial, we examined leukocyte differential counts and their relation to myocardial salvage and peak troponin T (TnT) in STEMI patients randomised to tocilizumab (n = 101) or placebo (n = 98). We performed RNA-sequencing on whole blood (n = 40) and T cells (n = 20). B and T cell subpopulations were examined by flow cytometry (n = 69). Findings (i) STEMI patients had higher neutrophil counts at hospitalisation compared with stable angina patients. (ii) After percutaneous coronary intervention there was a gradual decline in neutrophils, which was significantly more pronounced in the tocilizumab group. (iii) The decrease in neutrophils in the tocilizumab group was associated with improved myocardial salvage and lower peak TnT. (iv) RNA-sequencing suggested that neutrophil function was also attenuated by tocilizumab. (v) B and T cell sub-populations changed only minimally after STEMI with minor effects of tocilizumab, supported as well by RNA-sequencing analyses of T cells. (vi) However, a low CD8+ count was associated with improved myocardial salvage in patients admitted to the hospital > 3 h after symptom onset. Interpretation Tocilizumab induced a rapid reduction in neutrophils and seemed to attenuate neutrophil function in STEMI patients potentially related to the beneficial effects of tocilizumab on myocardial salvage. Funding South-Eastern Norway Regional Health Authority (Nos. 2019067, 2017084), the Central Norway Regional Health Authority and Norwegian Research Council (No. 283867).

ObjectivesWe aimed to report the angiographic and procedural results of the After Eighty study (ClinicalTrials.gov, NCT01255540), and to identify independent predictors of revascularisation.MethodsPatients of ≥80 years old with non-ST-elevation myocardial infarction and unstable angina pectoris were randomised to an invasive or conservative strategy. Angiographic and procedural results were recorded. Univariate and multivariate analyses were performed to explore variables predicting revascularisation.ResultsAmong 229 patients in the invasive group, 220 underwent immediate coronary angiography (90% performed via the radial artery). Of these patients, 48% had three-vessel disease or left main stenosis, 18% two-vessel disease, 16% one-vessel disease, 17% minor coronary vessel wall changes and two patients had normal coronary arteries. Six patients (3%) underwent coronary artery bypass graft. Percutaneous coronary intervention (PCI) was performed in 107 patients (49%), with 57% treated with bare metal stents, 37% drug-eluting stents and 6% balloon angioplasty. On average, 1.7 lesions were treated and 2 stents delivered per patient. Complications included 1 major PCI-related bleeding (successfully treated), 2 minor access site-related bleedings, 3 side branch occlusions during PCI and 11 periprocedural myocardial infarctions (considered end points). Sex, bundle branch block and smoking were independent predictors of revascularisation.ConclusionsPCI was performed in approximately half of the patients, similar to findings in younger populations. Procedural success was high, with few complications.Trial registration numberNCT01255540

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.