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

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

doi:10.1093/eurheartj/ehw171

Cited by 307 publications

(252 citation statements)

References 22 publications

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“…The design of the trial has been described previously 9. Patients between 18 and 80 years of age with NSTEMI presumed to be caused by CAD were eligible for inclusion.…”

Section: Methodsmentioning

confidence: 99%

“…In ACS, elevated levels of IL-6 and C reactive protein (CRP), the latter at least partly induced by IL-6,8 are related to adverse outcomes and the degree of myocardial injury 4. Furthermore, IL-6 seems to contribute to ischaemia/reperfusion injury in these patients 9. IL-6 is also associated with endothelial dysfunction in ACS,2 and may also contribute to enhanced expression of markers of endothelial cell activation such as cellular adhesion molecules (CAMs)10 and von Willebrand factor (vWF) 11.…”

Section: Introductionmentioning

confidence: 99%

“…In a randomised, double-blind, placebo-controlled trial, we recently showed that a single dose of tocilizumab attenuated the inflammatory response and percutaneous coronary intervention (PCI)-related troponin T (TnT) release in patients with non-ST-elevation myocardial infarction (NSTEMI) 9. In this predefined substudy, we sought to examine the effect of tocilizumab on coronary microvascular dysfunction and circulating markers of endothelial cell activation after NSTEMI.…”

Section: Introductionmentioning

confidence: 99%

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Effect of interleukin-6 inhibition on coronary microvascular and endothelial function in myocardial infarction

Holte

Kleveland²,

Ueland

et al. 2017

Heart

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“…The design of the trial has been described previously 9. Patients between 18 and 80 years of age with NSTEMI presumed to be caused by CAD were eligible for inclusion.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of interleukin-6 inhibition on coronary microvascular and endothelial function in myocardial infarction

Holte

Kleveland²,

Ueland

et al. 2017

Heart

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“…Targeting both the mPTP and improving plaque stability could be a strategy. Blocking IL-6, known to destabilize plaque in acute coronary syndromes, with the IL-6 receptor monoclonal antibody, tocilizumab, that also targets the mitochondria, has been shown to reduce infarct size in patients with non-ST-segment elevation myocardial infarction [54]. …”

Section: Discussionmentioning

confidence: 99%

Administration of the Mitochondrial Permeability Transition Pore Inhibitor, TRO40303, prior to Primary Percutaneous Coronary Intervention, Does Not Affect the Levels of Pro-Inflammatory Cytokines or Acute-Phase Proteins

Butt

Bache-Mathiesen²,

Nordrehaug³

et al. 2017

Cardiology

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Objectives: In the MITOCARE study, reperfusion injury was not prevented after administration of the mitochondrial permeability transition pore (mPTP) opening inhibitor, TRO40303, in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). The effects of TRO40303 on pro-inflammatory cytokines and acute-phase proteins were assessed. Methods: STEMI patients (n = 163, mean age 62 years) with chest pain within 6 h before admission for pPCI were randomized to intravenous bolus of TRO40303 (n = 83) or placebo (n = 80) prior to reperfusion. We tested whether the groups differed in levels of IL-1β, IL-6, IL-10, TNF, and high-sensitive C-reactive protein at various time points (0, 12, and 72 h) after PCI. Further, potential differences between groups in the change of biomarker levels between 0 and 72 h, 0 and 12 h, and 12 and 72 h were tested. Results: There were no statistically significant differences between the two groups, neither in levels of pro-inflammatory cytokines nor in levels of acute-phase proteins, and there were no statistically significant differences in the change of biomarker levels between the groups considering the time intervals from 0 to 72 h, from 0 to 12 h, and from 12 to 72 h. Conclusion: The administration of the mPTP, TRO40303, prior to reperfusion does not alter the pharmacokinetics of pro-inflammatory cytokines or acute-phase proteins during the first 72 h after PCI.

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“…19 Results from these trials showed a decrease in early CRP and troponin T release (a measure of myocardial damage), although coronary flow reserve (a measure of coronary microvascular function) was unaffected when assessed 6 months later. 19,20 The LDL cholesterol lowering drug Alirocumab (Praluent), 10 is also being tested in phase IV trials for use in non-ST segment elevation MI patients (NSTEMI) that have previously responded poorly to statins. Alirocumab will be administered as a single dose in acute MI, and LDL cholesterol and inflammatory markers measured up to 14 days after infarct.…”

Section: Myocardial Infarctionmentioning

confidence: 99%

Antibody Based Therapy in Coronary Artery Disease and Heart Failure

Fiedler¹

2017

Heart Res Open J

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The function of the immune system is to protect the host against disease. Antibodies are a key part of the adaptive response, recognising specific antigens and invading pathogens and marking them for destruction or blocking their activities. A mechanistic and molecular understanding of this process has allowed researchers to harness their natural function. They are now routinely used as a diagnostic tool in the clinic and in research to investigate pathological signalling. More recently, antibodies have been utilised for another application -therapy. Antibody based therapy is one of the newest and fastest growing with nearly 70 approved drugs to date and over 1000 in clinical trials. Investment from the pharmaceutical sector shows no signs of abating and this technology is now widely accepted for treating cancer, autoimmune and infectious diseases. In the context of the cardiovascular system however, antibody therapies are relatively limited. This review summarises the monoclonal antibodies approved for clinical use or currently in clinical trials for treating cardiovascular disorders. Presently, coronary artery disease, heart failure and transplant are the main indications, and monoclonal antibody therapies are discussed in the context of their specific applications.

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

Cited by 307 publications

References 22 publications

Effect of interleukin-6 inhibition on coronary microvascular and endothelial function in myocardial infarction

Effect of interleukin-6 inhibition on coronary microvascular and endothelial function in myocardial infarction

Administration of the Mitochondrial Permeability Transition Pore Inhibitor, TRO40303, prior to Primary Percutaneous Coronary Intervention, Does Not Affect the Levels of Pro-Inflammatory Cytokines or Acute-Phase Proteins

Antibody Based Therapy in Coronary Artery Disease and Heart Failure

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