Evidence map›Paper›PMID 25079365›Full record

Trial reportEuropean heart journal2015

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

Allison C Morton, Alexander M K Rothman, John P Greenwood, Julian Gunn, Alex Chase, Bernard Clarke, Alistair S Hall, Keith Fox, Claire Foley, Winston Banya and 3 more

Open access · hybridAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in European heart journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 190 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
190citing papers in PubMed, 7 pooled it
12.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

190 citing papers in PubMed, 7 syntheses or guidelines pooled it, 338 citations in OpenAlex.

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130 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 9 institutions in 1 country.

Allison C MortonDepartment of Cardiology, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
Alexander M K RothmanDepartment of Cardiology, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK Department of Cardiovascular Science, University of Sheffield, Sheffield, UK.
John P GreenwoodAcademic Unit of Cardiovascular Medicine, Yorkshire Heart Centre, Leeds, UK.
Julian GunnDepartment of Cardiology, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK Department of Cardiovascular Science, University of Sheffield, Sheffield, UK.
Alex ChaseAbertawe Bro Morgannwg University NHS Trust, Morriston Hospital, Swansea, UK.
Bernard ClarkeInstitute of Cardiovascular Sciences, University of Manchester, Manchester, UK.
Alistair S HallAcademic Unit of Cardiovascular Medicine, Yorkshire Heart Centre, Leeds, UK.
Keith FoxRoyal Infirmary of Edinburgh and University of Edinburgh, Edinburgh, UK.
Claire FoleyRoyal Brompton and Harefield NHS Foundation Trust and Imperial College London, London, UK.
Winston BanyaRoyal Brompton and Harefield NHS Foundation Trust and Imperial College London, London, UK.
Duolao WangDepartment of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
Marcus D FlatherRoyal Brompton and Harefield NHS Foundation Trust and Imperial College London, London, UK Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK.
David C CrossmanSchool of Medicine, University of St Andrews, KY16 9TF, UK dcc7@st-andrews.ac.uk.
Imperial College London · GBNorthern General Hospital · GBLiverpool School of Tropical Medicine · GBMorriston Hospital · GBRoyal Brompton & Harefield NHS Foundation Trust · GBUniversity of Edinburgh · GBUniversity of Manchester · GBUniversity of Sheffield · GBUniversity of St Andrews · GB

Funding

Medical Research Council G0502131Medical Research Council MR/K002406/1Medical Research Council MR/L01629X/1
6 · The paper itself

Abstract

aimsAcute 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

resultsA 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.

conclusionIL-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. CLINICAL TRIAL REGISTRATION EUCTR: 2006-001767-31-GB: www.clinicaltrialsregister.eu/ctr-search/trial/2006-001767-31/GB.

Indexed as

Acute Coronary SyndromeArea Under CurveBiomarkersC-Reactive ProteinDouble-Blind MethodFemaleHumansInterleukin 1 Receptor Antagonist ProteinInterleukin-6MaleMiddle AgedReceptors, Interleukin-1Treatment OutcomeTroponinvon Willebrand FactorBiomarkersC-Reactive ProteinInterleukin 1 Receptor Antagonist ProteinInterleukin-6Receptors, Interleukin-1Troponinvon Willebrand FactorDrugsInterleukinsMyocardial infarction

Identifiers

PMID25079365
PMCPMC4320321
OpenAlexW2165241435

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.