Effect of a single dose of the interleukin-6 receptor antagonist tocilizumab on inflammation and troponin T release in patients with non-ST-elevation myocardial infarction: a double-blind, randomized, placebo-controlled phase 2 trial

ObjectiveIt is unclear if activation of inflammatory pathways regulates proprotein convertase subtilisin-kexin type 9 (PCSK9) levels.ApproachWe evaluated (1) the temporal course of serum PCSK9 during hospitalisation following acute coronary syndrome and associations with markers of inflammation (leucocyte counts, interleukin (IL)-6, C-reactive protein) and lipid levels and (2) the effect of inhibition of IL-6 signalling with the IL-6 receptor antibody tocilizumab on PCSK9 levels in a randomised, double-blind, placebo-controlled trial release in patients with non-ST-elevation myocardial infarction.ResultsSerum PCSK9 increased during the acute phase and this response was modestly associated with neutrophil counts (r=0.24, p=0.009) and presence of hypercholesterolaemia (r=0.019, p=0.045), but was not modified by tocilizumab. However, a modifying effect of tocilizumab on PCSK9 levels was observed in patients with hypercholesterolaemia (p=0.024, repeated measures analysis of variance) and this effect was strongly correlated with the decrease in neutrophils (r=0.66, p=0.004).ConclusionsOur study suggests that patients with a more atherogenic profile may benefit from anti-IL-6 therapy with regard to PCSK9.Trial registration numberNCT01491074.

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Serum lipoprotein(a) is not modified by interleukin-6 receptor antagonism or associated with inflammation in non-ST-elevation myocardial infarction

International Journal of Cardiology ◽

10.1016/j.ijcard.2018.06.093 ◽

2019 ◽

Vol 274 ◽

pp. 348-350 ◽

Cited By ~ 4

Author(s):

Thor Ueland ◽

Ola Kleveland ◽

Annika E. Michelsen ◽

Rune Wiseth ◽

Jan Kristian Damås ◽

...

Keyword(s):

Myocardial Infarction ◽

Interleukin 6 ◽

Serum Lipoprotein ◽

St Elevation Myocardial Infarction ◽

Receptor Antagonism ◽

Lipoprotein A ◽

Interleukin 6 Receptor ◽

St Elevation

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Rationale for the ASSAIL-MI-trial: a randomised controlled trial designed to assess the effect of tocilizumab on myocardial salvage in patients with acute ST-elevation myocardial infarction (STEMI)

Open Heart ◽

10.1136/openhrt-2019-001108 ◽

2019 ◽

Vol 6 (2) ◽

pp. e001108 ◽

Cited By ~ 3

Author(s):

Anne Kristine Anstensrud ◽

Sindre Woxholt ◽

Kapil Sharma ◽

Kaspar Broch ◽

Bjørn Bendz ◽

...

Keyword(s):

Myocardial Infarction ◽

Infarct Size ◽

Troponin T ◽

Controlled Trial ◽

Experimental Studies ◽

Myocardial Necrosis ◽

Myocardial Salvage ◽

Ischaemia Reperfusion Injury ◽

Double Blind ◽

St Elevation

IntroductionInterleukin-6 (IL-6) may be involved in ischaemia-reperfusion injury and myocardial remodelling after myocardial infarction (MI). We have recently shown that IL-6 inhibition by tocilizumab attenuates systemic inflammation and troponin T-release in patients with acute non-ST elevation MI (NSTEMI). Experimental studies suggest that IL-6 inhibition can limit infarct size through anti-inflammatory mechanisms, but this has not been tested in clinical studies. With the ASSessing the effect of Anti-IL-6 treatment in MI (ASSAIL-MI) trial, we aim to examine whether a single administration of the IL-6 receptor antagonist tocilizumab can increase myocardial salvage in patients with acute ST-elevation MI (STEMI).Methods and analysisThe ASSAIL-MI trial is a randomised, double blind, placebo-controlled trial, conducted at three high-volume percutaneous coronary intervention (PCI) centres in Norway. 200 patients with first-time STEMI presenting within 6 hours of the onset of chest pain will be randomised to receive tocilizumab or matching placebo prior to PCI. The patients are followed-up for 6 months. The primary endpoint is the myocardial salvage index measured by cardiac MRI (CMR) 3–7 days after the intervention. Secondary endpoints include final infarct size measured by CMR and plasma markers of myocardial necrosis. Efficacy and safety assessments during follow-up include blood sampling, echocardiography and CMR.Ethics and disseminationBased on previous experience the study is considered feasible and safe. If tocilizumab increases myocardial salvage, further endpoint-driven multicentre trials may be initiated. The ASSAIL-MI trial has the potential to change clinical practice in patients with STEMI.RegistrationClinicaltrials.gov, identifier NCT03004703.

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