Evidence map›Paper›PMID 33099609›Full record

ReviewEuropean heart journal2021

Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine.

Rajiv Agarwal, Peter Kolkhof, George Bakris, Johann Bauersachs, Hermann Haller, Takashi Wada, Faiez Zannad

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

Review in European heart journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 301 papers, 15 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
301citing papers in PubMed, 15 pooled it
36.6field-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

301 citing papers in PubMed, 15 syntheses or guidelines pooled it, 538 citations in OpenAlex.

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  13. A European Renal Association (ERA) synopsis for nephrology practice of the 2023 European Society of Hypertension (ESH) Guidelines for the Management of Arterial Hypertension.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024
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241 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

7 authors at 6 institutions in 4 countries.

Rajiv AgarwalIndiana University School of Medicine and VA Medical Center, 1481 West 10th Street, 111N Indianapolis, IN 46202, USA.
Peter KolkhofR&D Preclinical Research Cardiovascular, Bayer AG, Wuppertal, Germany.
George BakrisAmerican Society of Hypertension's Comprehensive Hypertension Center at the University of Chicago Medicine, Chicago, IL, USA.
Johann BauersachsDepartment of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
Hermann HallerDepartment of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.
Takashi WadaDepartment of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Ishikawa, Japan.
Faiez ZannadCentre d'Investigations Cliniques Plurithématique, University Henri Poincaré, Nancy, France.
Medizinische Hochschule Hannover · DEBayer (Germany) · DEFrench Clinical Research Infrastructure Network · FRKanazawa University · JPRichard L. Roudebush VA Medical Center · USUniversity of Chicago · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This review covers the last 80 years of remarkable progress in the development of mineralocorticoid receptor (MR) antagonists (MRAs) from synthesis of the first mineralocorticoid to trials of nonsteroidal MRAs. The MR is a nuclear receptor expressed in many tissues/cell types including the kidney, heart, immune cells, and fibroblasts. The MR directly affects target gene expression-primarily fluid, electrolyte and haemodynamic homeostasis, and also, but less appreciated, tissue remodelling. Pathophysiological overactivation of the MR leads to inflammation and fibrosis in cardiorenal disease. We discuss the mechanisms of action of nonsteroidal MRAs and how they differ from steroidal MRAs. Nonsteroidal MRAs have demonstrated important differences in their distribution, binding mode to the MR and subsequent gene expression. For example, the novel nonsteroidal MRA finerenone has a balanced distribution between the heart and kidney compared with spironolactone, which is preferentially concentrated in the kidneys. Compared with eplerenone, equinatriuretic doses of finerenone show more potent anti-inflammatory and anti-fibrotic effects on the kidney in rodent models. Overall, nonsteroidal MRAs appear to demonstrate a better benefit-risk ratio than steroidal MRAs, where risk is measured as the propensity for hyperkalaemia. Among patients with Type 2 diabetes, several Phase II studies of finerenone show promising results, supporting benefits on the heart and kidneys. Furthermore, finerenone significantly reduced the combined primary endpoint (chronic kidney disease progression, kidney failure, or kidney death) vs. placebo when added to the standard of care in a large Phase III trial.

Indexed as

Diabetes Mellitus, Type 2Heart FailureHumansMineralocorticoid Receptor AntagonistsMineralocorticoidsSpironolactoneMineralocorticoid Receptor AntagonistsMineralocorticoidsSpironolactoneCardiorenalChronic kidney diseaseFinerenoneMineralocorticoid receptor antagonistsMineralocorticoids

Identifiers

PMID33099609
PMCPMC7813624
OpenAlexW3093851112

What Socratic holds

Textmetadata
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 Socratic graph.