Evidence map›Paper›PMID 33972404›Full record

Trial reportOpen heart2021

Tocilizumab increases citrullinated histone 3 in non-ST segment elevation myocardial infarction.

Ragnhild Helseth, Ola Kleveland, Thor Ueland, Rune Wiseth, Jan Kristian Damas, Kaspar Broch, Annika Michelsen, Bjørn Bendz, Lars Gullestad, Pål Aukrust and 1 more

Open access · goldAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Open heart, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 35% 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

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
  2. NETosis Markers, Such as Citrullinated Histones, Myeloperoxidase, and Elastase, should not be Recommended as Predictors of COVID-19 Severity.Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Ragnhild HelsethCenter for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway ragnhild.helseth@gmail.com.ORCID 0000-0001-5012-9214
Ola KlevelandClinic of Cardiology, St. Olavs Hospital, Trondheim, Norway.
Thor UelandInstitute of Clinical Medicine, University of Oslo, Oslo, Norway.
Rune WisethClinic of Cardiology, St. Olavs Hospital, Trondheim, Norway.
Jan Kristian DamasDepartment of Infectious Diseases, St Olavs Hospital, Trondheim, Trondheim, Norway.
Kaspar BrochDepartment of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Annika MichelsenInstitute of Clinical Medicine, University of Oslo, Oslo, Norway.
Bjørn BendzDepartment of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.ORCID 0000-0002-1392-6481
Lars GullestadInstitute of Clinical Medicine, University of Oslo, Oslo, Norway.
Pål AukrustInstitute of Clinical Medicine, University of Oslo, Oslo, Norway.
Ingebjørg SeljeflotCenter for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway.
Oslo University Hospital · NOSt Olav's University Hospital · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveBeyond reducing inflammation and troponin T (TnT) release, the interleukin-6 receptor antagonist tocilizumab reduces neutrophil counts in patients with non-ST segment elevation myocardial infarction (NSTEMI). It is unclear if this is related to formation of neutrophil extracellular traps (NETs), carrying inflammatory and thrombotic properties.

methodsIn a placebo-controlled trial, 117 patients with NSTEMI were randomised to a single dose of tocilizumab (n=58) or placebo (n=59) before coronary angiography. The NETs related markers double-stranded DNA (dsDNA), myloperoxidase-DNA (MPO-DNA) and citrullinated histone 3 (H3Cit) were measured at five consecutive time points during hospitalisation (days 1-3).

resultsOur major findings were: (1) H3Cit levels were significantly higher in the tocilizumab compared with the placebo group at all time points (all p<0.05), and H3Cit area under the curve (AUC) was 2.3 fold higher in the tocilizumab compared with placebo group (p<0.0001). (2) MPO-DNA and dsDNA did not differ between the groups. (3) In both treatment arms, dsDNA AUC was associated with TnT AUC. (4) Neutrophil count AUC correlated inversely to H3Cit AUC (p=0.015) in the total population.

conclusionsIn patients with NSTEMI, treatment with tocilizumab is associated with increased circulating H3Cit levels, suggesting that tocilizumab enhances NETosis. Further studies should clarify whether NETosis is a relevant side effect of tocilizumab. Regardless of tocilizumab, dsDNA associated with TnT release, indicating a link between extracellular nuclear material and myocardial injury.

Indexed as

AdolescentAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedBiomarkersDose-Response Relationship, DrugDouble-Blind MethodFemaleHistonesHumansMaleMiddle AgedNon-ST Elevated Myocardial InfarctionTroponin TYoung AdultAntibodies, Monoclonal, HumanizedBiomarkersHistonestocilizumabTroponin Tcoronary artery diseaseinflammationmyocardial infarction

Identifiers

PMID33972404
PMCPMC8112443
OpenAlexW3162129354

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.