title: 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.
abstract: Interleukin-6 (IL-6) contributes to atherosclerotic plaque destabilization and is involved in myocardial injury during ischaemia-reperfusion. Interleukin-6 is therefore a potential therapeutic target in myocardial infarction (MI). We hypothesized that the IL-6 receptor antagonist tocilizumab would attenuate inflammation, and secondarily reduce troponin T (TnT) release in non-ST-elevation MI (NSTEMI).
  
  
  
  In a two-centre, double-blind, placebo-controlled trial, 117 patients with NSTEMI were randomized at a median of 2 days after symptom onset to receive placebo (n = 59) or tocilizumab (n = 58), administered as a single dose prior to coronary angiography. High sensitivity (hs) C-reactive protein and hsTnT were measured at seven consecutive timepoints between Days 1 and 3. The area under the curve (AUC) for high-sensitivity C-reactive protein was the primary endpoint. The median AUC for high-sensitivity C-reactive protein during hospitalization was 2.1 times higher in the placebo than in the tocilizumab group (4.2 vs. 2.0 mg/L/h, P < 0.001). Also, the median AUC for hsTnT during hospitalization was 1.5 times higher in the placebo group compared with the tocilizumab group (234 vs. 159 ng/L/h, P = 0.007). The differences between the two treatment groups were observed mainly in (i) patients included ≤2 days from symptom onset and (ii) patients treated with percutaneous coronary intervention (PCI). No safety issues in the tocilizumab group were detected during 6 months of follow-up.
  
  
  
  Tocilizumab attenuated the inflammatory response and primarily PCI-related TnT release in NSTEMI patients.
authors.affiliation: Clinic of Cardiology, St Olavs Hospital, Trondheim, Norway Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway ola.kleveland@ntnu.no.
authors.forename: Ola
authors.initials: O
authors.lastname: Kleveland
authors.affiliation: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Gabor
authors.initials: G
authors.lastname: Kunszt
authors.affiliation: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Marte
authors.initials: M
authors.lastname: Bratlie
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Oslo, Norway K.G. Jebsen Centre of Inflammatory Research, University of Oslo, Oslo, Norway K.G. Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway.
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.affiliation: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway K.G. Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway.
authors.forename: Kaspar
authors.initials: K
authors.lastname: Broch
authors.affiliation: Clinic of Cardiology, St Olavs Hospital, Trondheim, Norway Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Espen
authors.initials: E
authors.lastname: Holte
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Annika E
authors.initials: AE
authors.lastname: Michelsen
authors.affiliation: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Bendz
authors.affiliation: Clinic of Cardiology, St Olavs Hospital, Trondheim, Norway Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Brage H
authors.initials: BH
authors.lastname: Amundsen
authors.affiliation: Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Terje
authors.initials: T
authors.lastname: Espevik
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Svend
authors.initials: S
authors.lastname: Aakhus
authors.affiliation: Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Jan Kristian
authors.initials: JK
authors.lastname: Damås
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Oslo, Norway K.G. Jebsen Centre of Inflammatory Research, University of Oslo, Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Clinic of Cardiology, St Olavs Hospital, Trondheim, Norway Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Rune
authors.initials: R
authors.lastname: Wiseth
authors.affiliation: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Oslo, Norway K.G. Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway Centre for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
mesh_terms: D061067:Antibodies, Monoclonal, Humanized; D004311:Double-Blind Method; D006801:Humans; D007249:Inflammation; D000072658:Non-ST Elevated Myocardial Infarction; D019947:Receptors, Interleukin-6; D020107:Troponin T
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D019947:Receptors, Interleukin-6; D020107:Troponin T; C502936:tocilizumab
keywords: Acute coronary syndromes; Inflammation; Interleukin-6; Myocardial infarction; Tocilizumab