Evidence map›Paper›PMID 25176015›Full record

Trial reportThe New England journal of medicine2014

Angiotensin-neprilysin inhibition versus enalapril in heart failure.

John J V McMurray, Milton Packer, Akshay S Desai, Jianjian Gong, Martin P Lefkowitz, Adel R Rizkala, Jean L Rouleau, Victor C Shi, Scott D Solomon, Karl Swedberg and 2 more

21 registry-linked trialsOpen access · bronzeAbstract readComparative StudyMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The New England journal of medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 21 registered trials, which are not on this map. Cited by 2,692 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2,692citing papers in PubMed, 12 pooled it
242.4field-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.

NCT07379788 nacompletedstarted 2025, after this paper: background citation

Mitral Remodeling Index: A Novel Composite Measure the Effect of ARNI Alone Versus ARNI Combined With SGLT2 Inhibitors on Functional Mitral Regurgitation Remodeling.

Ran2025Enrolled180Registered outcomes4Posted comparisons0ConditionsHeart FailureArmsEmpagliflozin10Mg Tab, Sacubitril/Valsartan 49 MG-51 MG Oral Tablet [ENTRESTO]
PMID 30132036other papers from this trial
Open the trial in the graph
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
NCT03832660 phase2completednot on this mapstarted 2019, after this paper: background citation

Clinical and Genetic Determinants of Disease Progression and Response to Sacubitril/Valsartan vs Lifestyle (Physical Activity and Dietary Nitrate) in Patients With Hypertrophic Cardiomyopathy

TypeinterventionalSponsorNewcastle UniversityRan2019 to 2022Enrolled168ConditionsHypertrophic CardiomyopathyArmsLifestyle, Sacubitril/Valsartan
NCT04113109 phase4completednot on this mapstarted 2019, after this paper: background citation

Mechanisms Underlying Hypotensive Response to ARB/NEP Inhibition - Aim 2

TypeinterventionalSponsorVanderbilt University Medical CenterRan2019 to 2025Enrolled46ConditionsHeart FailureArmsLCZ 696, Icatibant, placebo, Para-aminohippurate, Iohexol
NCT04128891 phase3withdrawnnot on this mapstarted 2020, after this paper: background citation

PRospectIve Study of Sacubitril/ValsarTan on MyocardIal OxygenatioN and Fibrosis in PatiEnts With Heart Failure and Preserved Ejection Fraction

TypeinterventionalSponsorFlinders UniversityRan2020 to 2024Enrolled0ConditionsHeart Failure With Preserved Ejection FractionArmsSacubitril-Valsartan
NCT04191681 phase4recruitingnot on this mapstarted 2019, after this paper: background citation

Safety and Efficacy of Angiotensin Receptor-neprilysin Inhibitor After Left Ventricular Assist Device ImplanT (SEAL-IT) Study

TypeinterventionalSponsorThe Cleveland ClinicRan2019 to 2022Enrolled50ConditionsStage D Heart FailureArmsSacubitril-Valsartan, Usual care (standard-of-care) arm
NCT04197050 phase4unknown statusnot on this mapstarted 2020, after this paper: background citation

Effect of Sacubitril/Valsartan on Right Ventricular Dysfunctioning Patients With Connective Tissue Disease

TypeinterventionalSponsorRenJi HospitalRan2020 to 2022Enrolled60ConditionsMyocardial Injury, Connective Tissue DiseasesArmsSacubitril / Valsartan Oral Tablet
NCT04235062 nacompletednot on this mapstarted 2020, after this paper: background citation

NATriuretic Response to Expansion and dIUretics in huMans With Heart Failure

TypeinterventionalSponsorMomentum Research, Inc.Ran2020 to 2021Enrolled229ConditionsHeart FailureArmsRinger's (8.6 g/L sodium chloride, 0.33 g/L calcium chloride, 0.3 g/L potassium chloride) Solution, Intravenous Bolus Furosemide
NCT04397302 completednot on this mapstarted 2019, after this paper: background citation

Reverse Remodeling is Associated With Hemodynamic Improvement and Stabilization in Outpatients With Heart Failure With Reduced Ejection Fraction Treated With Sacubitril/Valsartan: an Echocardiographic Study

Typeobservational_patient_registrySponsorItalian Society of CardiologyRan2019 to 2020Enrolled652ConditionsHeart Failure, Left Sided, Left Ventricular Dysfunction, Ventricular RemodelingArmsRole of Sacubitril/Valsartan in Hemodynamic and Echocardiographic Improvement of Heart Failure With Reduced Ejection Fraction
NCT04458285 naunknown statusnot on this mapstarted 2020, after this paper: background citation

A Multi-center, Randomized, Open-label, Active-controlled, 12-week Study to Evaluate the Efficacy and Safety of Sacubitril/Valsartan in Maintenance Hemodialysis Patients With Heart Failure

TypeinterventionalSponsorGuangdong Provincial People's HospitalRan2020 to 2020Enrolled118ConditionsHemodialysis Complication, Heart FailureArmsSacubitril / Valsartan Oral Tablet [Entresto], Valsartan 80mg Tablet
NCT04649229 phase4completednot on this mapstarted 2021, after this paper: background citation

Mechanisms Underlying Hypotensive Response to ARB/NEP Inhibition - Aim 3

TypeinterventionalSponsorYale UniversityRan2021 to 2025Enrolled46ConditionsHeart FailureArmsLCZ 696, Placebo, Para-aminohippurate, Iohexol, Aprepitant
NCT04853758 phase3unknown statusnot on this mapstarted 2021, after this paper: background citation

Angiotensin Receptor-Neprilysin Inhibition in Chagas Cardiomyopathy With Reduced Ejection Fraction: Randomized Trial ANSWER-HF

TypeinterventionalSponsorUniversity of Sao Paulo General HospitalRan2021 to 2024Enrolled200ConditionsChagas CardiomyopathyArmsSacubitril / Valsartan Oral Tablet [Entresto], Enalapril
NCT05002075 nacompletednot on this mapstarted 2021, after this paper: background citation

Efficacy of an m-Health Cardiac Rehabilitation Program in Heart Failure With Preserved Ejection Fraction: A Pilot Randomized Controlled Trial

TypeinterventionalSponsorUniversity of Texas Southwestern Medical CenterRan2021 to 2024Enrolled69ConditionsHeart Failure With Preserved Ejection FractionArmsm-health cardiac rehabilitation
NCT05366101 phase2 / phase3completednot on this mapstarted 2019, after this paper: background citation

Clinical and Genetic Determinants of Disease Progression and Response to Lifestyle and Pharmacological Interventions in Patients With Hypertrophic Cardiomyopathy

TypeinterventionalSponsorNewcastle-upon-Tyne Hospitals NHS TrustRan2019 to 2022Enrolled168ConditionsHypertrophic CardiomyopathyArmsSacubitril/Valsartan, Lifestyle
NCT05498181 phase2completednot on this mapstarted 2022, after this paper: background citation

Angiotensin-Neprilysin Inhibition in Hemodialysis Initiation

TypeinterventionalSponsorBrigham and Women's HospitalRan2022 to 2026Enrolled45ConditionsHemodialysisArmsSacubitril-valsartan, Placebo
NCT05964738 phase2completednot on this mapstarted 2022, after this paper: background citation

Safety and Tolerability of Diuretics Withdrawal in Heart Failure With Reduced Ejection Fraction. REDICAE Trial.

TypeinterventionalSponsorMaimónides Biomedical Research Institute of CórdobaRan2022 to 2024Enrolled98ConditionsHeart Failure, Electric Impedance, Dyspnea, SafetyArmsDiuretics withdrawal, Diuretics maintenance
NCT06062316 unknown statusnot on this mapstarted 2022, after this paper: background citation

Early Warning Model of Myocardial Remodeling After Acute Myocardial Infarction Based on Multimodal Feature Structure Technology

TypeobservationalSponsorXuanwu Hospital, BeijingRan2022 to 2024Enrolled4,000ConditionsMyocardial Infarction
NCT06503445 nacompletednot on this mapstarted 2021, after this paper: background citation

The Impact of Video-based Cardiac Rehabilitation Education in Patients With Cardiovascular Implantable Electronic Devices(CIEDs)- a Randomized Controlled Trial

TypeinterventionalSponsorNational Taiwan University Hospital Hsin-Chu BranchRan2021 to 2022Enrolled85ConditionsPatients With Cardiac Implantable Electronic DevicesArmseducation video
NCT06675448 recruitingnot on this mapstarted 2021, after this paper: background citation

In Search of Best Practices for Patients With Heart Failure and Secondary Mitral Regurgitation: An Evaluation of the Inova Heart Failure Treatment Algorithm

Typeobservational_patient_registrySponsorInova Health Care ServicesRan2021 to 2030Enrolled50ConditionsMitral Regurgitation, Valvular Heart Disease, Heart FailureArmsMitraClip, Moderate MR
NCT06704633 phase4recruitingnot on this mapstarted 2026, after this paper: background citation

Health Status After Switching Angiotensin-converting Enzyme Inhibitors or Angiotensin Receptor Blockers to Sacubitril-valsartan in Patients With Heart Failure With Reduced Ejection Fraction From Rural Tanzania: An Interventional Study

TypeinterventionalSponsorMartin RohacekRan2026 to 2028Enrolled298ConditionsHeart FailureArmsSacubitril / Valsartan Oral Tablet
NCT07481825 nanot yet recruitingnot on this mapstarted 2026, after this paper: background citation

Impact of Combined cARdio-pUlmonary aSsessment on COPD Clinical Management: the ICARUS Study

TypeinterventionalSponsorUniversity of Bari Aldo MoroRan2026 to 2029Enrolled350ConditionsCOPD (Chronic Obstructive Pulmonary Disease), Cardiovascular DiseaseArmsStructured combined cardio-pulmonary clinical management strategy, Standard Respiratory Management
3 · Its place in the literature

Who cites it

2,692 citing papers in PubMed, 12 syntheses or guidelines pooled it, 6,700 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Guideline
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Pooled it
  10. Pooled it
  11. Pooled it
  12. Pooled it
  13. Trial
  14. Trial
  15. Trial
  16. Trial
  17. Trial
  18. Trial
  19. Trial
  20. Trial

2,632 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 5 institutions in 4 countries.

John J V McMurrayFrom the British Heart Foundation (BHF) Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (J.J.V.M.); the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.); the Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston (A.S.D., S.D.S.); Novartis Pharmaceuticals, East Hanover, NJ (J.G., M.P.L., A.R.R., V.C.S.); Institut de Cardiologie de Montréal, Université de Montréal, Montreal (J.L.R.); the Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden (K.S.); National Heart and Lung Institute, Imperial College London, London (K.S.); and the Medical University of South Carolina and Ralph H. Johnson Veterans Affairs Medical Center, Charleston (M.R.Z.).
Milton Packer
Akshay S Desai
Jianjian Gong
Martin P Lefkowitz
Adel R Rizkala
Jean L Rouleau
Victor C Shi
Scott D Solomon
Karl Swedberg
Michael R Zile
PARADIGM-HF Investigators and Committees
Brigham and Women's Hospital · USImperial College London · GBMontreal Heart Institute · CARalph H. Johnson VA Medical Center · USThe University of Texas Southwestern Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWe compared the angiotensin receptor-neprilysin inhibitor LCZ696 with enalapril in patients who had heart failure with a reduced ejection fraction. In previous studies, enalapril improved survival in such patients.

methodsIn this double-blind trial, we randomly assigned 8442 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either LCZ696 (at a dose of 200 mg twice daily) or enalapril (at a dose of 10 mg twice daily), in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure, but the trial was designed to detect a difference in the rates of death from cardiovascular causes.

resultsThe trial was stopped early, according to prespecified rules, after a median follow-up of 27 months, because the boundary for an overwhelming benefit with LCZ696 had been crossed. At the time of study closure, the primary outcome had occurred in 914 patients (21.8%) in the LCZ696 group and 1117 patients (26.5%) in the enalapril group (hazard ratio in the LCZ696 group, 0.80; 95% confidence interval [CI], 0.73 to 0.87; P<0.001). A total of 711 patients (17.0%) receiving LCZ696 and 835 patients (19.8%) receiving enalapril died (hazard ratio for death from any cause, 0.84; 95% CI, 0.76 to 0.93; P<0.001); of these patients, 558 (13.3%) and 693 (16.5%), respectively, died from cardiovascular causes (hazard ratio, 0.80; 95% CI, 0.71 to 0.89; P<0.001). As compared with enalapril, LCZ696 also reduced the risk of hospitalization for heart failure by 21% (P<0.001) and decreased the symptoms and physical limitations of heart failure (P=0.001). The LCZ696 group had higher proportions of patients with hypotension and nonserious angioedema but lower proportions with renal impairment, hyperkalemia, and cough than the enalapril group.

conclusionsLCZ696 was superior to enalapril in reducing the risks of death and of hospitalization for heart failure. (Funded by Novartis; PARADIGM-HF ClinicalTrials.gov number, NCT01035255.).

Indexed as

AgedAminobutyratesAngiotensin-Converting Enzyme InhibitorsAngiotensin Receptor AntagonistsBiphenyl CompoundsDouble-Blind MethodDrug CombinationsEnalaprilFemaleHeart FailureHospitalizationHumansKaplan-Meier EstimateMaleMiddle AgedNeprilysinAminobutyratesAngiotensin-Converting Enzyme InhibitorsAngiotensin Receptor AntagonistsBiphenyl CompoundsDrug CombinationsEnalaprilNeprilysinsacubitril and valsartan sodium hydrate drug combinationTetrazolesValsartan

Identifiers

PMID25176015
OpenAlexW2113698123

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

and 15 more above

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.