Evidence map›Paper›PMID 30846338›Full record

Trial reportJournal of the American College of Cardiology2019

B-Type Natriuretic Peptide During Treatment With Sacubitril/Valsartan: The PARADIGM-HF Trial.

Peder Langeland Myhre, Muthiah Vaduganathan, Brian Claggett, Milton Packer, Akshay S Desai, Jean L Rouleau, Michael R Zile, Karl Swedberg, Martin Lefkowitz, Victor Shi and 2 more

Registry-linked trialOpen access · greenAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of the American College of Cardiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01035255 (A Multicenter, Randomized, Double-blind, Parallel Group, Active-controlled Study to Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality in Patients With Chronic Heart Failure and Reduced Ejection Fraction), which is not on this map. Cited by 107 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed, 4 pooled it
17.5field-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.

NCT01035255 phase3terminatednot on this map

A Multicenter, Randomized, Double-blind, Parallel Group, Active-controlled Study to Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality in Patients With Chronic Heart Failure and Reduced Ejection Fraction

TypeinterventionalSponsorNovartis PharmaceuticalsRan2009 to 2014Enrolled8,442ConditionsHeart Failure With Reduced Ejection FractionArmsLCZ696 200 mg BID, Enalapril 10 mg BID
3 · Its place in the literature

Who cites it

107 citing papers in PubMed, 4 syntheses or guidelines pooled it, 190 citations in OpenAlex.

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  13. Cardiac Biomarkers in Chronic Kidney Disease: Signal or Noise?Clinical journal of the American Society of Nephrology : CJASN · 2026
    Review
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47 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 8 institutions in 5 countries.

Peder Langeland MyhreCardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts; Division of Medicine, Akershus University Hospital and University of Oslo, Oslo, Norway. Electronic address: https://twitter.com/pmyhre.
Muthiah VaduganathanCardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: https://twitter.com/mvaduganathan.
Brian ClaggettCardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
Milton PackerBaylor University Medical Center, Dallas, Texas.
Akshay S DesaiCardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
Jean L RouleauMontreal Heart Institute and University of Montreal, Montreal, Quebec, Canada.
Michael R ZileMedical University of South Carolina and Ralph H. Johnson Veterans Administration Medical Center, Charleston, South Carolina.
Karl SwedbergUniversity of Gothenburg, Gothenburg, Sweden.
Martin LefkowitzNovartis Pharmaceuticals Corporation, East Hanover, New Jersey.
Victor ShiNovartis Pharmaceuticals Corporation, East Hanover, New Jersey.
John J V McMurrayUniversity of Glasgow, Glasgow, United Kingdom.
Scott D SolomonCardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: ssolomon@rics.bwh.harvard.edu.
Brigham and Women's Hospital · USNovartis (United States) · USTwitter (United States) · USBaylor University Medical Center · USMedical University of South Carolina · USMontreal Heart Institute · CAUniversity of Glasgow · GBUniversity of Gothenburg · SE

Funding

The Harvard Clinical and Translational Science CenterUL1TR002541 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2018 to 2022
$93.0M
NCATS NIH HHS UL1 TR002541
6 · The paper itself

Abstract

backgroundNatriuretic peptides are substrates of neprilysin; hence, B-type natriuretic peptide (BNP) concentrations rise with neprilysin inhibition. Thus, the clinical validity of measuring BNP in sacubitril/valsartan-treated patients has been questioned, and use of N-terminal pro-B-type natriuretic peptides (NT-proBNP) has been preferred and recommended.

objectivesThe purpose of this study was to determine the prognostic performance of BNP measurements before and during treatment with sacubitril/valsartan.

methodsBNP and NT-proBNP were measured before and after 4 to 6 weeks, 8 to 10 weeks, and 9 months of treatment with sacubitril/valsartan in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. We assessed the association of levels of these natriuretic peptides with the subsequent risk of cardiovascular death or hospitalization for HF.

resultsMedian BNP concentration (before treatment: 202 ng/l [Q1 to Q3: 126 to 335 ng/l]) increased to 235 ng/l (Q1 to Q3: 128 to 422 ng/l) after 8 to 10 weeks of treatment. BNP concentrations doubled in 141 (18%) patients and tripled in 49 (6%) patients during the first 8 to 10 weeks of sacubitril/valsartan. In contrast, such striking increases in NT-proBNP following the use of the neprilysin inhibitor were extremely rare. Treatment with sacubitril/valsartan caused a rightward shift in the distribution of BNP when compared with NT-proBNP, but both peptides retained their prognostic accuracy (C-statistics of 63% to 67% for BNP and C-statistics of 64% to 70% for NT-proBNP) with no difference between the 2 biomarkers. Increases in both BNP and NT-proBNP during 8 to 10 weeks of sacubitril/valsartan were associated with worse outcomes (p = 0.003 and p = 0.005, respectively).

conclusionsCirculating levels of BNP may increase meaningfully early after initiation of sacubitril/valsartan. In comparison, NT-proBNP is not a substrate of neprilysin inhibition, and thus may lead to less clinical confusion when measured within 8 to 10 weeks of drug initiation. However, during treatment, either biomarker predicts the risk of major adverse outcomes in patients treated with angiotensin receptor-neprilysin inhibitors. (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255).

Indexed as

AgedAminobutyratesAngiotensin Receptor AntagonistsBiomarkersBiphenyl CompoundsDrug CombinationsFemaleHeart FailureHumansMaleMiddle AgedNatriuretic Peptide, BrainPeptide FragmentsProspective StudiesTetrazolesValsartanAminobutyratesAngiotensin Receptor AntagonistsBiomarkersBiphenyl CompoundsDrug CombinationsNatriuretic Peptide, BrainPeptide Fragmentspro-brain natriuretic peptide (1-76)sacubitril and valsartan sodium hydrate drug combinationTetrazolesValsartanbiomarkerheart failurenatriuretic peptidesprognosticationrisk stratificationtreatment

Identifiers

PMID30846338
PMCPMC7955687
OpenAlexW2918599246

What OpenQuestion holds

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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.