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

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 a...

Full description

Saved in:
Bibliographic Details
Published in:European heart journal 2016-08, Vol.37 (30), p.2406-2413
Main Authors: Kleveland, Ola, Kunszt, Gabor, Bratlie, Marte, Ueland, Thor, Broch, Kaspar, Holte, Espen, Michelsen, Annika E, Bendz, Bjørn, Amundsen, Brage H, Espevik, Terje, Aakhus, Svend, Damås, Jan Kristian, Aukrust, Pål, Wiseth, Rune, Gullestad, Lars
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal, Humanized
Double-Blind Method
Humans
Inflammation
Non-ST Elevated Myocardial Infarction
Receptors, Interleukin-6
Troponin T
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0195-668X
1522-9645
DOI:10.1093/eurheartj/ehw171