Evidence map›Paper›PMID 30702995›Full record

ReviewCirculation research2019

Anticytokine Agents: Targeting Interleukin Signaling Pathways for the Treatment of Atherothrombosis

Paul M Ridker

Open access · bronzeAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Circulation research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
140citing papers in PubMed, 7 pooled it
13.5field-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

140 citing papers in PubMed, 7 syntheses or guidelines pooled it, 258 citations in OpenAlex.

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

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

1 author at 1 institution in 1 country.

Paul M RidkerFrom the Center for Cardiovascular Disease Prevention, Divisions of Cardiovascular Medicine and Preventive Medicine, Brigham and Women's Hospital, Boston, MA.
Brigham and Women's Hospital · US

Funding

Cardiovascular Inflammation Reduction Trial (CIRT)U01HL101422 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI RIDKER, PAUL M. · 2011 to 2018
$55.4M
NHLBI NIH HHS U01 HL101422
6 · The paper itself

Abstract

The recognition that atherosclerosis is a complex chronic inflammatory disorder mediated through both adaptive and innate immunity has led to the hypothesis that anticytokine therapies targeting specific IL (interleukin) signaling pathways could serve as powerful adjuncts to lipid lowering in the prevention and treatment of cardiovascular disease. Cytokines involved in human atherosclerosis can be broadly classified as proinflammatory and proatherogenic (such as IL-1, IL-6, and TNF [tumor necrosis factor]) or as anti-inflammatory and antiatherogenic (such as IL-10 and IL-1rA). The recent CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) has shown that specific targeting of IL-1β can significantly reduce cardiovascular event rates without lipid or blood pressure lowering. In CANTOS, the magnitude of benefit of this cytokine-targeted approach to atherosclerosis treatment was associated to the magnitude of reduction of the central signaling cytokine IL-6 and the downstream clinical biomarker high-sensitivity CRP (C-reactive protein). By contrast, in the recent CIRT (Cardiovascular Inflammation Reduction Trial), low-dose methotrexate neither reduced IL-1β, IL-6, or high-sensitivity CRP nor lowered cardiovascular event rates. Taken together, these 2 contemporary trials provide proof of principle that focused cytokine inhibition, not broad-spectrum anti-inflammatory therapy, is likely to be crucial for atheroprotection. This review provides an overview of cytokines in atherosclerosis, the potential benefits and risks associated with targeted anticytokine therapies, and a look to the future of clinical practices addressing residual inflammatory risk.

Indexed as

Interleukin-6 InhibitorsAnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAtherosclerosisCardiovascular DiseasesCD40 AntigensCD40 LigandC-Reactive ProteinDiabetes Mellitus, Type 2Disease Models, AnimalHematopoiesisHumansInflammasomesInterleukin-18Interleukin-1betaAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedcanakinumabCD40 AntigensCD40 LigandC-Reactive ProteinInflammasomesInterleukin-18Interleukin-1betaInterleukin-6 InhibitorsMethotrexateNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanTriggering Receptor Expressed on Myeloid Cells-1cardiovascular diseasescytokineshumansinflammasomesinterleukins

Identifiers

PMID30702995
PMCPMC6386195
OpenAlexW2914237180

What OpenQuestion holds

Textmetadata
LicenceTDM
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.