Evidence mapPaperPMID 39873282Full record

Trial reportEuropean heart journal2025

Near-universal prevalence of central adiposity in heart failure with preserved ejection fraction: the PARAGON-HF trial.

Alexander Peikert, Muthiah Vaduganathan, Brian L Claggett, Ian J Kulac, Sheldon Litwin, Michael Zile, Akshay S Desai, Pardeep S Jhund, Jawad H Butt, Carolyn S P Lam and 8 more

Erratum issued Registry-linked trialAbstract readRandomized Controlled TrialMulticenter Study
In one paragraph

Trial report in European heart journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT01920711 (A Multicenter, Randomized, Double-blind, Parallel Group, Active-controlled Study to Evaluate the Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients), which is not on this map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
field-weighted citation impact
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.

NCT01920711 phase3completednot on this map

A Multicenter, Randomized, Double-blind, Parallel Group, Active-controlled Study to Evaluate the Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients (NYHA Class II-IV) With Preserved Ejection Fraction (PARAGON-HF)

TypeinterventionalSponsorNovartis PharmaceuticalsRan2014 to 2019Enrolled4,822ConditionsHeart Failure With Preserved Ejection FractionArmsLCZ696, Valsartan
3 · Its place in the literature

Who cites it

41 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Alexander PeikertCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-0947-5865
Muthiah VaduganathanCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-0885-1953
Brian L ClaggettCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-4215-9218
Ian J KulacCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Sheldon LitwinCardiovascular Division, Medical University of South Carolina and Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA.
Michael ZileCardiovascular Division, Medical University of South Carolina and Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA.
Akshay S DesaiCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-1443-0701
Pardeep S JhundBritish Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
Jawad H ButtBritish Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
Carolyn S P LamNational Heart Centre, Duke-National University of Singapore, Singapore, Singapore.ORCID 0000-0003-1903-0018
Felipe MartinezNational University of Cordoba, Cordoba, Argentina.
Dirk J Van VeldhuisenDepartment of Cardiology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.
Faiez ZannadInserm, Centre d'Investigation Clinique Plurithématique 1433, U1116, CHRU de Nancy, F-CRIN INI-CRCT Université de Lorraine, Nancy, France.ORCID 0000-0001-7456-1570
Jean RouleauInstitut de Cardiologie de Montréal, Université de Montréal, Montreal, QC, Canada.
Martin LefkowitzNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
John J V McMurrayBritish Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
Scott D SolomonCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-3698-9597
Milton PackerBaylor University Medical Center, 621 N. Hall Street, Dallas, TX 75226, USA.ORCID 0000-0003-1828-2387

Funding

Novartis
6 · The paper itself

Abstract

BACKGROUND AND

aimsAn expansion of fat mass is an integral feature of patients with heart failure and preserved ejection fraction (HFpEF). While body mass index (BMI) is the most common anthropometric measure, a measure of central adiposity-the waist-to-height ratio (WHtR)-focuses on body fat content and distribution; is not distorted by bone or muscle mass, sex, or ethnicity; and may be particularly relevant in HFpEF.

methodsThe PARAGON-HF trial randomized 4796 patients with heart failure (HF) and ejection fraction ≥45% to valsartan or sacubitril/valsartan. The current work characterizes the association of BMI and WHtR with clinical features, outcomes, and the response to neprilysin inhibition.

resultsAbout half (49%) of the participants were considered obese by BMI (≥30 kg/m2), but nearly every patient (96%) had central adiposity (WHtR ≥.5). Among patients who were not obese (BMI <30 kg/m2), 860 (37%) had marked central adiposity (WHtR ≥.6). Higher BMI and WHtR were both associated with higher risk of total HF hospitalizations, but as compared with BMI, WHtR was linearly associated with HF outcomes and identified a higher proportion of patients who had a particularly elevated risk (i.e. 30% or greater). An obesity-survival paradox (i.e. improved outcomes in those with greater adiposity) was apparent with BMI in unadjusted analyses, but it was not observed with WHtR. Although neprilysin inhibition appeared to have greater effects on HF outcomes in patients with higher BMI and WHtR, analyses of interaction with obesity metrics did not show significant heterogeneity across the range of values for adiposity.

conclusionsIn PARAGON-HF, in contrast with BMI, nearly every patient with HFpEF had central adiposity (as assessed by WHtR), and the risks of adverse HF events were more robustly related to WHtR. These data challenge the current reliance on BMI as an appropriate metric of adiposity, and they suggest that-rather than obesity-related HFpEF being regarded as a select HFpEF subgroup-central adiposity is a ubiquitous feature of HFpEF. CLINICAL

trial registrationhttps://www.clinicaltrials.gov. Unique identifier: NCT01920711.

Indexed as

Heart FailureObesity, AbdominalAdiposityAgedAminobutyratesAngiotensin Receptor AntagonistsBiphenyl CompoundsBody Mass IndexDrug CombinationsFemaleHospitalizationHumansMaleMiddle AgedNeprilysinStroke VolumeAminobutyratesAngiotensin Receptor AntagonistsBiphenyl CompoundsDrug CombinationsNeprilysinsacubitril and valsartan sodium hydrate drug combinationTetrazolesValsartanAngiotensin receptor–neprilysin inhibitorBody mass indexHeart failure with preserved ejection fractionObesityWaist-to-height ratio

Identifiers

PMID39873282
PMCPMC12208775

What Socratic holds

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LicenceCC BY-NC
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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 Socratic graph.