ReviewJACC. Basic to translational science2023
Neprilysin Inhibitors in Heart Failure: The Science, Mechanism of Action, Clinical Studies, and Unanswered Questions.
Review in JACC. Basic to translational science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Ten years real-world experience with sacubitril/valsartan in patients with heart failure with reduced ejection fraction.ESC heart failure · 2026Pooled it
- Long-Term Control of Refractory Cardiogenic Pleural Effusion in a Cat Treated with Sacubitril/Valsartan and Hydrochlorothiazide: A Case Report.Animals : an open access journal from MDPI · 2026Article
- Neprilysin mediated cleavage of phospholamban dysregulates SERCA in heart failure.bioRxiv : the preprint server for biology · 2026Article
- Acute myocardial infarction in a patient with HAM/TSP evaluated for circulatory dynamics during mobilization before and after antihypertensive drug modification: a case report.Journal of medical case reports · 2026Article
- Protection against isoproterenol-induced cardiac injury by sacubitril/valsartan is associated with upregulation of the alternative renin-angiotensin-aldosterone system pathway.Scientific reports · 2026Article
- Cardiorenal and Metabolic Dimensions of Cardiomyopathies and Heart Failure: Focus on SGLT2i, GLP1-RA, and ns-MRA.Current cardiology reports · 2026Review
- Sacubitril/valsartan facilitates recovery of cardiac function in a patient with peripartum cardiomyopathy: a case report.European heart journal. Case reports · 2026Article
- Targeting Neuropeptide Y: Novel Approaches to the Treatment of Cardiovascular and Haematological Disorders.Cardiovascular & hematological disorders drug targets · 2026Review
- Retrospective real-world study on effectiveness and safety of sacubitril/valsartan in Indian patients with heart failure.American journal of cardiovascular disease · 2026Article
- Impact of sacubitril/valsartan on cardiac structure and function in post-acute myocardial infarction heart failure patients aged over 65: a single-center experience.American journal of translational research · 2026Article
- Empagliflozin-pirfenidone dual therapy improves cardiac function and structure in a preclinical two-hit HFpEF model.Frontiers in pharmacology · 2026Article
- Angiotensin receptor-neprilysin inhibitors improve the outcome of lung cancer patients with hypertension undergoing immune checkpoint inhibitors treatment.BMC cardiovascular disorders · 2025Article
- Obesity Is Associated with a Lower Risk of Mortality and Readmission in Heart Failure Patients with Diabetes.Biomedicines · 2025Article
- Heart Failure in the Modern Era: A Narrative Overview of Recent Research from 2022-2025.Journal of cardiovascular development and disease · 2025Review
- Lowly Expressed Toxin Transcripts in Poorly Characterized Myanmar Russell's Viper Venom Gland.Biotech (Basel (Switzerland)) · 2025Article
- Location and aetiology are determinants of fibroblast activation and heterogeneity in the failing human heart.Genome medicine · 2025Article
- Effect of Sacubitril/Valsartan, Ivabradine, and Captopril on Anxiety-like Behavior in Spontaneously Hypertensive Rats.International journal of molecular sciences · 2025Article
- Urinary markers in heart failure - types, timing and thresholds. European Journal of Heart Failure expert consensus document.European journal of heart failure · 2025Review
- Cardiac fibrosis: from mechanisms and models to medicines.Trends in pharmacological sciences · 2025Review
- Neprilysin regulates the progression of glioblastoma: an in-vitro study using siRNA mediated gene silencing and HDAC1 mediated upregulation of neprilysin in U87 MG cells.Molecular and cellular biochemistry · 2025Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This article provides a contemporary review and a new perspective on the role of neprilysin inhibition in heart failure (HF) in the context of recent clinical trials and addresses potential mechanisms and unanswered questions in certain HF patient populations. Neprilysin is an endopeptidase that cleaves a variety of peptides such as natriuretic peptides, bradykinin, adrenomedullin, substance P, angiotensin I and II, and endothelin. It has a broad role in cardiovascular, renal, pulmonary, gastrointestinal, endocrine, and neurologic functions. The combined angiotensin receptor and neprilysin inhibitor (ARNi) has been developed with an intent to increase vasodilatory natriuretic peptides and prevent counterregulatory activation of the angiotensin system. ARNi therapy is very effective in reducing the risks of death and hospitalization for HF in patients with HF and New York Heart Association functional class II to III symptoms, but studies failed to show any benefits with ARNi when compared with angiotensin-converting enzyme inhibitors or angiotensin receptor blocker in patients with advanced HF with reduced ejection fraction or in patients following myocardial infarction with left ventricular dysfunction but without HF. These raise the questions about whether the enzymatic breakdown of natriuretic peptides may not be a very effective solution in advanced HF patients when there is downstream blunting of the response to natriuretic peptides or among post-myocardial infarction patients in the absence of HF when there may not be a need for increased natriuretic peptide availability. Furthermore, there is a need for additional studies to determine the long-term effects of ARNi on albuminuria, obesity, glycemic control and lipid profile, blood pressure, and cognitive function in patients with HF.
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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 OpenQuestion graph.