Evidence map›Paper›PMID 26663387›Full record

Trial reportBritish journal of clinical pharmacology2016

The effect of LCZ696 (sacubitril/valsartan) on amyloid-β concentrations in cerebrospinal fluid in healthy subjects.

Thomas H Langenickel, Chiaki Tsubouchi, Surya Ayalasomayajula, Parasar Pal, Marie-Anne Valentin, Markus Hinder, Stanford Jhee, Hakop Gevorkyan, Iris Rajman

Open access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in British journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 2 pooled it
9.6field-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

46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 109 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Trial
  4. Trial
  5. Observational
  6. Article
  7. Article
  8. Review
  9. Review
  10. Review
  11. Review
  12. Sacubitril/valsartan and the risk of incident dementia in heart failure: a nationwide propensity-matched cohort study.Clinical research in cardiology : official journal of the German Cardiac Society · 2024
    Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Review
  18. Review
  19. Angiotensin receptor-neprilysin inhibitors: Comprehensive review and implications in hypertension treatment.Hypertension research : official journal of the Japanese Society of Hypertension · 2021
    Review
  20. Sympathetic modulation by antihypertensive drugs.Journal of clinical hypertension (Greenwich, Conn.) · 2021
    Article
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

9 authors at 4 institutions in 4 countries.

Thomas H LangenickelTranslational Medicine, Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland.
Chiaki TsubouchiTranslational Medicine, Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland.
Surya AyalasomayajulaDrug Metabolism and Pharmacokinetics, Novartis Institutes for Biomedical Research, East Hanover, New Jersey, USA.
Parasar PalBiostatistical Sciences, Integrated Development Functions and Regions, Novartis Healthcare Pvt Ltd, Hyderabad, India.
Marie-Anne ValentinTranslational Medicine, Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland.
Markus HinderTranslational Medicine, Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland.
Stanford JheePAREXEL International, Glendale, California, USA.
Hakop GevorkyanCalifornia Clinical Trials Medical Group in Affiliation with PAREXEL International, Glendale, California, USA.
Iris RajmanTranslational Medicine, Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland.
Novartis (Switzerland) · CHNovartis (India) · INPAREXEL International (United Kingdom) · GBPAREXEL International (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsLCZ696 (angiotensin receptor neprilysin inhibitor) is a novel drug developed for the treatment of heart failure with reduced ejection fraction. Neprilysin is one of multiple enzymes degrading amyloid-β (Aβ). Its inhibition may increase Aβ levels. The potential exists that treatment of LCZ696, through the inhibition of neprilysin by LBQ657 (an LCZ696 metabolite), may result in accumulation of Aβ. The aim of this study was to assess the blood-brain-barrier penetration of LBQ657 and the potential effects of LCZ696 on cerebrospinal fluid (CSF) concentrations of Aβ isoforms in healthy human volunteers.

methodsIn a double-blind, randomized, parallel group, placebo-controlled study, healthy subjects received once daily LCZ696 (400 mg, n = 21) or placebo (n = 22) for 14 days.

resultsLCZ696 had no significant effect on CSF AUEC(0,36 h) of the aggregable Aβ species 1-42 or 1-40 compared with placebo (estimated treatment ratios 0.98 [95% CI 0.73, 1.34; P = 0.919] and 1.05 [95% CI 0.82, 1.34; P = 0.702], respectively). A 42% increase in CSF AUEC(0,36 h) of soluble Aβ 1-38 was observed (estimated treatment ratio 1.42 [95% CI 1.05, 1.91; P = 0.023]). CSF levels of LBQ657 and CSF Aβ 1-42, 1-40, and 1-38 concentrations were not related (r(2) values 0.022, 0.010, and 0.008, respectively).

conclusionsLCZ696 did not cause changes in CSF levels of aggregable Aβ isoforms (1-42 and 1-40) compared with placebo, despite achieving CSF concentrations of LBQ657 sufficient to inhibit neprilysin. The clinical relevance of the increase in soluble CSF Aβ 1-38 is currently unknown.

Indexed as

AdolescentAdultAminobutyratesAmyloid beta-PeptidesAngiotensin Receptor AntagonistsBiphenyl CompoundsBlood-Brain BarrierDouble-Blind MethodDrug CombinationsFemaleHealthy VolunteersHeart FailureHumansMaleMiddle AgedNeprilysinAminobutyratesAmyloid beta-PeptidesAngiotensin Receptor AntagonistsBiphenyl CompoundsDrug CombinationsLBQ657Neprilysinsacubitril and valsartan sodium hydrate drug combinationTetrazolesValsartanamyloid-βCSFheart failureLCZ696neprilysin

Identifiers

PMID26663387
PMCPMC4834603
OpenAlexW2202895441

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.