title: 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: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
  2006-001767-31-GB: www.clinicaltrialsregister.eu/ctr-search/trial/2006-001767-31/GB.
authors: Department of Cardiology, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
authors: Allison C
authors: AC
authors: Morton
authors: Department of Cardiology, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK Department of Cardiovascular Science, University of Sheffield, Sheffield, UK.
authors: Alexander M K
authors: AM
authors: Rothman
authors: Academic Unit of Cardiovascular Medicine, Yorkshire Heart Centre, Leeds, UK.
authors: John P
authors: JP
authors: Greenwood
authors: Department of Cardiology, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK Department of Cardiovascular Science, University of Sheffield, Sheffield, UK.
authors: Julian
authors: J
authors: Gunn
authors: Abertawe Bro Morgannwg University NHS Trust, Morriston Hospital, Swansea, UK.
authors: Alex
authors: A
authors: Chase
authors: Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK.
authors: Bernard
authors: B
authors: Clarke
authors: Academic Unit of Cardiovascular Medicine, Yorkshire Heart Centre, Leeds, UK.
authors: Alistair S
authors: AS
authors: Hall
authors: Royal Infirmary of Edinburgh and University of Edinburgh, Edinburgh, UK.
authors: Keith
authors: K
authors: Fox
authors: Royal Brompton and Harefield NHS Foundation Trust and Imperial College London, London, UK.
authors: Claire
authors: C
authors: Foley
authors: Royal Brompton and Harefield NHS Foundation Trust and Imperial College London, London, UK.
authors: Winston
authors: W
authors: Banya
authors: Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
authors: Duolao
authors: D
authors: Wang
authors: Royal Brompton and Harefield NHS Foundation Trust and Imperial College London, London, UK Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK.
authors: Marcus D
authors: MD
authors: Flather
authors: School of Medicine, University of St Andrews, KY16 9TF, UK dcc7@st-andrews.ac.uk.
authors: David C
authors: DC
authors: Crossman
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D019540:Area Under Curve; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome; D014336:Troponin / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D017472:Receptors, Interleukin-1; D014336:Troponin; D014841:von Willebrand Factor; D002097:C-Reactive Protein
keywords: Drugs; Interleukins; Myocardial infarction