Evidence map›Paper›PMID 30520545›Full record

ArticleEuropean journal of heart failure2019

Effects of sacubitril/valsartan on neprilysin targets and the metabolism of natriuretic peptides in chronic heart failure: a mechanistic clinical study.

Hélène Nougué, Théo Pezel, François Picard, Malha Sadoune, Mattia Arrigo, Florence Beauvais, Jean-Marie Launay, Alain Cohen-Solal, Nicolas Vodovar, Damien Logeart

Registry-linked trialOpen access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in European journal of heart failure, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05580510 ("An Open-label Clinical Trial to Evaluate the Safety and Efficacy of Empagliflozin and Sacubitril/Valsartan in Adult Patients With Chronic Heart Failure With Reduced Ejection Fraction Associated With Congenital Heart Disease"), which is not on this map. Cited by 84 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed, 3 pooled it
12.5field-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.

NCT05580510 phase2 / phase3unknown statusstarted 2023, after this paper: background citation

"An Open-label Clinical Trial to Evaluate the Safety and Efficacy of Empagliflozin and Sacubitril/Valsartan in Adult Patients With Chronic Heart Failure With Reduced Ejection Fraction Associated With Congenital Heart Disease"

Ran2023Enrolled160Registered outcomes9Posted comparisons0ConditionsCongenital Heart Disease, Heart Failure, Heart Failure With Reduced Ejection FractionArmsEmpagliflozin 10 MG OD, Sacubitril 49 MG / Valsartan 51 MG [Entresto] BID
PMID 33447845PMID 30415601PMID 32865377PMID 33030857PMID 33186500PMID 33832352PMID 33960724PMID 34447992PMID 26787434PMID 26787728other papers from this trial
Open the trial in the graph
3 · Its place in the literature

Who cites it

84 citing papers in PubMed, 3 syntheses or guidelines pooled it, 147 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 7 institutions in 2 countries.

Hélène NouguéInserm UMR-S 942, Lariboisière Hospital, Paris, France.
Théo PezelInserm UMR-S 942, Lariboisière Hospital, Paris, France.
François PicardHeart Failure Unit, Haut-Lévêque Hospital, Pessac, France.
Malha SadouneInserm UMR-S 942, Lariboisière Hospital, Paris, France.
Mattia ArrigoDepartment of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland.
Florence BeauvaisDepartment of Cardiology, Lariboisière Hospital, Paris, France.
Jean-Marie LaunayInserm UMR-S 942, Lariboisière Hospital, Paris, France.
Alain Cohen-SolalInserm UMR-S 942, Lariboisière Hospital, Paris, France.
Nicolas VodovarInserm UMR-S 942, Lariboisière Hospital, Paris, France.
Damien LogeartInserm UMR-S 942, Lariboisière Hospital, Paris, France.
Hôpital Lariboisière · FRInserm · FRDélégation Paris 7 · FRHôpital Cardiologique du Haut-Lévêque · FRSorbonne Paris Cité · FRUniversité Paris Cité · FRUniversity Hospital of Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimThis study aimed at evaluating the effects of sacubitril/valsartan on neprilysin (NEP), and the metabolism of natriuretic peptides in heart failure (HF) and providing additional mechanistic information on the mode of action of the drug. METHODS AND

resultsWe enrolled 73 chronic HF patients who were switched from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to sacubitril/valsartan. In addition to clinical and echocardiographic assessment, plasma biomarkers were measured at baseline, day 30 and day 90 after initiation of treatment. Sacubitril/valsartan led to decrease in New York Heart Association class and improvement of echocardiographic parameters, as well as a dose-dependent decrease in soluble NEP (sNEP) activity, while sNEP concentration remained unchanged. Neprilysin inhibition translated into an increase in its substrates such as atrial natriuretic peptide (ANP), substance P, and glucagon-like peptide 1, the latter translating into a decrease in fructosamine. Cardiac troponin and soluble ST2 levels, biomarkers of HF severity unrelated to NEP metabolism also decreased. While there was a ∼4-fold increase in ANP, we observed no change in plasma brain natriuretic peptide (BNP) and plasma BNP activity, and a mild decrease in N-terminal proBNP (NT-proBNP) concentrations. Finally, we found a progressive increase in the relationship between BNP and NT-proBNP, which strongly correlated with an increase in T71 proBNP glycosylation (R

conclusionSacubitril/valsartan rapidly and strongly reduced sNEP activity, leading to an increase in levels of NEP substrates. These data suggest a pleiotropic favourable impact of sacubitril/valsartan on the metabolism of HF patients with ANP rather than BNP as major effectors amongst natriuretic peptides.

Indexed as

AgedAminobutyratesAngiotensin Receptor AntagonistsAtrial Natriuretic FactorBiphenyl CompoundsCD146 AntigenChronic DiseaseDose-Response Relationship, DrugDrug CombinationsEchocardiographyFemaleFructosamineGlucagon-Like Peptide 1Heart FailureHumansInterleukin-1 Receptor-Like 1 ProteinAminobutyratesAngiotensin Receptor AntagonistsAtrial Natriuretic FactorBiphenyl CompoundsCD146 AntigenDrug CombinationsFructosamineGlucagon-Like Peptide 1IL1RL1 protein, humanInterleukin-1 Receptor-Like 1 ProteinMCAM protein, humanNatriuretic Peptide, BrainNeprilysinPeptide Fragmentspro-brain natriuretic peptide (1-76)sacubitril and valsartan sodium hydrate drug combinationSubstance PTetrazolesTroponin IValsartanAtrial natriuretic peptideBrain natriuretic peptideHeart failure with reduced ejection fractionNeprilysinSacubitril/valsartan

Identifiers

PMID30520545
OpenAlexW2903958160

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

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.