The effect of interleukin-1 receptor antagonist therapy on markers of inflammation in non-ST elevation acute coronary syndromes: the MRC-ILA Heart Study

Morton, A. C., Rothman, A. M. K., Greenwood, J. P., Gunn, J., Chase, A., Clarke, B., Hall, A. S., Fox, K., Foley, C., Banya, W., Wang, Duolao ORCID: https://orcid.org/0000-0003-2788-2464, Flather, M. D. and Crossman, D. C. (2014) 'The effect of interleukin-1 receptor antagonist therapy on markers of inflammation in non-ST elevation acute coronary syndromes: the MRC-ILA Heart Study'. European Heart Journal, Vol 36, Issue 6, pp. 377-384.

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Abstract

Aims
Acute coronary syndromes (ACSs) are driven by inflammation within coronary plaque. Interleukin-1 (IL-1) has an established role in atherogenesis and the vessel-response to injury. ACS patients have raised serum markers of inflammation. We hypothesized that if IL-1 is a driving influence of inflammation in non-ST elevation ACS (NSTE-ACS), IL-1 inhibition would reduce the inflammatory response at the time of ACS.

Methods and results
A phase II, double-blinded, randomized, placebo-controlled, study recruited 182 patients with NSTE-ACS, presenting <48 h from onset of chest pain. Treatment was 1:1 allocation to daily, subcutaneous IL-1receptor antagonist (IL-1ra) or placebo for 14 days. Baseline characteristics were well matched. Treatment compliance was 85% at 7 days. The primary endpoint (area-under-the-curve for C-reactive protein over the first 7 days) was: IL-1ra group, 21.98 mg day/L (95%CI 16.31–29.64); placebo group, 43.5 mg day/L (31.15–60.75) (geometric mean ratio = 0.51 mg/L; 95%CI 0.32–0.79; P = 0.0028). In the IL-1ra group, 14-day achieved high-sensitive C-reactive protein (P < 0.0001) and IL-6 levels (P = 0.02) were lower than Day 1. Sixteen days after discontinuation of treatment (Day 30) high-sensitive C-reactive protein levels had risen again in the IL-1ra group [IL-1ra; 3.50 mg/L (2.65–4.62): placebo; 2.21 mg/L (1.67–2.92), P = 0.022]. MACE at Day 30 and 3 months was similar but at 1 year there was a significant excess of events in the IL-1ra group.

Conclusion
IL-1 drives C-reactive protein elevation at the time of NSTE-ACS. Following 14 days IL-1ra treatment inflammatory markers were reduced. These results show the importance of IL-1 as a target in ACS, but also indicate the need for additional studies with anti-IL-1 therapy in ACS to assess duration and safety.

Item Type:	Article
Subjects:	QV Pharmacology > QV 38 Drug action. QW Microbiology and Immunology > Immunity by Type > QW 568 Cellular immunity. Immunologic cytotoxicity. Immunocompetence. Immunologic factors (General) WG Cardiovascular System > Heart. Heart Diseases > WG 200 General works
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1093/eurheartj/ehu272
Depositing User:	Lynn Roberts-Maloney
Date Deposited:	14 Jan 2015 11:31
Last Modified:	06 Sep 2019 15:26
URI:	https://archive.lstmed.ac.uk/id/eprint/4739

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