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

Eur Heart J. 2016 Aug 7;37(30):2406-13. doi: 10.1093/eurheartj/ehw171. Epub 2016 May 8.

Abstract

Aims: 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).

Methods and results: 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.

Conclusion: Tocilizumab attenuated the inflammatory response and primarily PCI-related TnT release in NSTEMI patients.

Keywords: Acute coronary syndromes; Inflammation; Interleukin-6; Myocardial infarction; Tocilizumab.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Antibodies, Monoclonal, Humanized
  • Double-Blind Method
  • Humans
  • Inflammation
  • Non-ST Elevated Myocardial Infarction*
  • Receptors, Interleukin-6
  • Troponin T

Substances

  • Antibodies, Monoclonal, Humanized
  • Receptors, Interleukin-6
  • Troponin T
  • tocilizumab