Evidence map›Paper›PMID 40265590›Full record

Trial reportJournal of the American Heart Association2025

Comprehensive Analysis of the Effects of Sacubitril/Valsartan According to Sex Among Patients With Heart Failure and Reduced Ejection Fraction in PARADIGM-HF.

Misato Chimura, Jawad H Butt, Shingo Matsumoto, Eoghan G M McMurray, Alasdair D Henderson, Atefeh Talebi, Akshay S Desai, Martin P Lefkowitz, Adel R Rizkala, Jean L Rouleau and 6 more

Registry-linked trialAbstract readClinical Trial, Phase IIIComparative StudyMulticenter Study
In one paragraph

Trial report in Journal of the American Heart Association, 2025. 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 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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.

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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
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

16 authors.

Misato ChimuraBritish Heart Foundation Cardiovascular Research Centre University of Glasgow UK.
Jawad H ButtBritish Heart Foundation Cardiovascular Research Centre University of Glasgow UK.
Shingo MatsumotoBritish Heart Foundation Cardiovascular Research Centre University of Glasgow UK.
Eoghan G M McMurrayBritish Heart Foundation Cardiovascular Research Centre University of Glasgow UK.
Alasdair D HendersonBritish Heart Foundation Cardiovascular Research Centre University of Glasgow UK.ORCID 0000-0002-8903-4906
Atefeh TalebiBritish Heart Foundation Cardiovascular Research Centre University of Glasgow UK.ORCID 0000-0002-8144-9074
Akshay S DesaiDivision of Cardiovascular Medicine Brigham and Women's Hospital Boston MA USA.ORCID 0000-0002-1443-0701
Martin P LefkowitzNovartis East Hanover NJ USA.ORCID 0000-0002-8830-6316
Adel R RizkalaNovartis East Hanover NJ USA.ORCID 0000-0002-4118-4489
Jean L RouleauInstitut de Cardiologie de Montréal Université de Montréal Montreal QC Canada.ORCID 0000-0002-5353-3877
Scott D SolomonDivision of Cardiovascular Medicine Brigham and Women's Hospital Boston MA USA.ORCID 0000-0003-3698-9597
Karl SwedbergDepartment of Molecular and Clinical Medicine University of Gothenburg Sweden.ORCID 0000-0002-6358-2154
Michael R ZileMedical University of South Carolina and Ralph H. Johnson Veterans Administration Medical Center Charleston SC USA.ORCID 0000-0001-7076-221X
Milton PackerBaylor Heart and Vascular Institute Baylor University Medical Center Dallas TX USA.ORCID 0000-0003-1828-2387
Pardeep S JhundBritish Heart Foundation Cardiovascular Research Centre University of Glasgow UK.ORCID 0000-0003-4306-5317
John J V McMurrayBritish Heart Foundation Cardiovascular Research Centre University of Glasgow UK.ORCID 0000-0002-6317-3975

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWomen with heart failure (HF) ejection fraction appeared to respond more favorably to sacubitril/valsartan, compared with valsartan, than men in PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction), driven by a greater reduction in total (first and recurrent) HF hospitalizations. Sex-specific efficacy and safety of sacubitril/valsartan in PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) remain unreported. METHODS AND

resultsThis post hoc analysis of PARADIGM-HF examined sex-based outcomes in patients with HF and reduced ejection fraction randomized to sacubitril/valsartan or enalapril. The primary end point was a composite of cardiovascular death or HF hospitalization. Secondary and exploratory efficacy outcomes, biomarker changes, and safety outcomes were also assessed. Among 8399 participants, 1832 (21.8%) were women. Women were older, had worse New York Heart Association functional class and Kansas City Cardiomyopathy Questionnaire scores, more symptoms of HF, and lower estimated glomerular filtration rate, yet had lower rates of HF hospitalization (and other worsening of HF) and cardiovascular death than men. Compared with enalapril, sacubitril/valsartan reduced the risk of the primary end point to a similar extent in both sexes: hazard ratios, 0.76 (95% CI, 0.62-0.94) in women and 0.80 (95% CI, 0.73-0.89) in men (

conclusionsIn PARADIGM-HF, sacubitril/valsartan, compared with enalapril, reduced the risk of HF hospitalizations, death from cardiovascular causes, and death from any cause similarly in women and men with HF with reduced ejection fraction. In addition, sacubitril/valsartan was safe and well tolerated, irrespective of sex. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT01035255.

Indexed as

AminobutyratesAngiotensin Receptor AntagonistsHeart FailureStroke VolumeTetrazolesValsartanVentricular Function, LeftAgedBiphenyl CompoundsDrug CombinationsEnalaprilFemaleHospitalizationHumansMaleMiddle AgedAminobutyratesAngiotensin Receptor AntagonistsBiphenyl CompoundsDrug CombinationsEnalaprilsacubitril and valsartan sodium hydrate drug combinationTetrazolesValsartanheart failure hospitalizationheart failure with reduced ejection fraction (HFrEF)prognosissacubitril/valsartansex differencestreatment effect

Identifiers

PMID40265590
PMCPMC12334938

What Socratic holds

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LicenceCC BY-NC
Read underepoch 390

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.