The effect of interleukin-1 receptor antagonist therapy on markers of inflammation in non-ST elevation acute coronary syndromes : the MRC-ILA Heart Study
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.
Citation
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 , D , Flather , M D & Crossman , D C 2015 , ' 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 , no. 6 , pp. 377-384 . https://doi.org/10.1093/eurheartj/ehu272
Publication
European Heart Journal
Status
Peer reviewed
ISSN
0195-668XType
Journal article
Description
This work was supported by UK Medical Research Council Experimental Medicine Grant number G0502131 and a UK Medical Research Council Clinical Research Training Fellowship MR/K002406/1 (A.M.K.R.). IL-1ra (Anakinra) and matching placebo were donated by Amgen Corporation. Funding to pay the Open Access publication charges for this article was provided by the University of Sheffield.Collections
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