Evidence map›Paper›PMID 27974807›Full record

ReviewNature reviews. Cardiology2017

Long-term neprilysin inhibition - implications for ARNIs.

Duncan J Campbell

Abstract readReview
PubMed Publisher
In one paragraph

Review in Nature reviews. Cardiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 5 pooled it
5.2field-weighted citation impact, top 4% 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

78 citing papers in PubMed, 5 syntheses or guidelines pooled it, 148 citations in OpenAlex.

  1. Pooled it
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  6. Trial
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  13. Cross talk on therapeutic strategies: natriuretic peptides and inhibiting neprilysin in hypertension management.Hypertension research : official journal of the Japanese Society of Hypertension · 2025
    Review
  14. Article
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  16. Review
  17. Article
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  20. Advancing Guideline-Directed Medical Therapy in Heart Failure: Overcoming Challenges and Maximizing Benefits.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2024
    Review

18 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.

Duncan J CampbellSt Vincent's Institute of Medical Research, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia.
University of Melbourne · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neprilysin has a major role in both the generation and degradation of bioactive peptides. LCZ696 (valsartan/sacubitril, Entresto), the first of the new ARNI (dual-acting angiotensin-receptor-neprilysin inhibitor) drug class, contains equimolar amounts of valsartan, an angiotensin-receptor blocker, and sacubitril, a prodrug for the neprilysin inhibitor LBQ657. LCZ696 reduced blood pressure more than valsartan alone in patients with hypertension. In the PARADIGM-HF study, LCZ696 was superior to the angiotensin-converting enzyme inhibitor enalapril for the treatment of heart failure with reduced ejection fraction, and LCZ696 was approved by the FDA for this purpose in 2015. This approval was the first for chronic neprilysin inhibition. The many peptides metabolized by neprilysin suggest many potential consequences of chronic neprilysin inhibitor therapy, both beneficial and adverse. Moreover, LBQ657 might inhibit enzymes other than neprilysin. Chronic neprilysin inhibition might have an effect on angio-oedema, bronchial reactivity, inflammation, and cancer, and might predispose to polyneuropathy. Additionally, inhibition of neprilysin metabolism of amyloid-β peptides might have an effect on Alzheimer disease, age-related macular degeneration, and cerebral amyloid angiopathy. Much of the evidence for possible adverse consequences of chronic neprilysin inhibition comes from studies in animal models, and the relevance of this evidence to humans is unknown. This Review summarizes current knowledge of neprilysin function and possible consequences of chronic neprilysin inhibition that indicate a need for vigilance in the use of neprilysin inhibitor therapy.

Indexed as

Heart FailureAminobutyratesAngiotensin Receptor AntagonistsAnimalsBiological AvailabilityBiphenyl CompoundsBlood PressureDrug CombinationsHumansNeprilysinStroke VolumeTetrazolesValsartanAminobutyratesAngiotensin Receptor AntagonistsBiphenyl CompoundsDrug CombinationsLBQ657Neprilysinsacubitril and valsartan sodium hydrate drug combinationTetrazolesValsartan

Identifiers

PMID27974807
OpenAlexW2562411701

What OpenQuestion holds

Textmetadata
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.