Evidence map›Paper›PMID 30741494›Full record

Trial reportEuropean journal of heart failure2019

Reduced loop diuretic use in patients taking sacubitril/valsartan compared with enalapril: the PARADIGM-HF trial.

Orly Vardeny, Brian Claggett, Jessica Kachadourian, Akshay S Desai, Milton Packer, Jean Rouleau, Michael R Zile, Karl Swedberg, Martin Lefkowitz, Victor Shi and 2 more

2 registry-linked trialsOpen access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in European journal of heart failure, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 77 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 3 pooled it
16.3field-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.

NCT04397302 completednot on this map

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
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
3 · Its place in the literature

Who cites it

77 citing papers in PubMed, 3 syntheses or guidelines pooled it, 172 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Highlights in heart failure.ESC heart failure · 2019
    Pooled it
  4. Trial
  5. Trial
  6. Trial
  7. Diuretic therapy as prognostic enrichment factor for clinical trials in patients with heart failure with reduced ejection fraction.Clinical research in cardiology : official journal of the German Cardiac Society · 2021
    Trial
  8. Trial
  9. Diuretics in Cardiovascular Disease: For How Long and at What Dose?Journal of cardiovascular development and disease · 2026
    Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Review
  18. High-intensity care for GDMT titration.Heart failure reviews · 2024
    Review
  19. Article
  20. Review

17 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 9 institutions in 4 countries.

Orly VardenyCenter for Care Delivery and Outcomes Research, VA Health Care System, Minneapolis, MN, USA.
Brian ClaggettDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard University, Boston, MA, USA.
Jessica KachadourianNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Akshay S DesaiDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard University, Boston, MA, USA.
Milton PackerBaylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX, USA.
Jean RouleauMontreal Heart Institute and University of Montreal, Montreal, Québec, Canada.
Michael R ZileDepartment of Medicine, Medical University of South Carolina, and the RHJ Department of Veterans Affairs Medical Center, Charleston, SC, USA.
Karl SwedbergDepartment of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
Martin LefkowitzNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Victor ShiNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
John J V McMurrayBritish Heart Foundation and Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
Scott D SolomonDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard University, Boston, MA, USA.
Tris Pharma (United States) · USBrigham and Women's Hospital · USBaylor University Medical Center · USBritish Heart Foundation · GBHarvard University · USMedical University of South Carolina · USUniversité de Montréal · CAUniversity of Gothenburg · SEUniversity of Minnesota · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsTo assess differences in diuretic dose requirements in patients treated with sacubitril/valsartan compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial. METHODS AND

resultsOverall, 8399 patients with New York Heart Association class II-IV heart failure and reduced LVEF were randomized to sacubitril/valsartan 200 mg bid or enalapril 10 mg twice daily. Loop diuretic doses were assessed at baseline, 6, 12, and 24 months, and furosemide dose equivalents were calculated via multiplication factors (2x for torsemide and 40x for bumetanide). Percentages of participants with reductions or increases in loop diuretic dose were determined. At baseline, 80.8% of participants were taking any diuretics (n = 6290 for loop diuretics, n = 496 for other diuretics); of those, recorded dosage data for loop diuretics were available on 5487 participants. Mean baseline furosemide equivalent doses were 48.2 mg for sacubitril/valsartan and 49.6 mg for enalapril (P = 0.25). Patients treated with sacubitril/valsartan were more likely to reduce diuretic dose and less likely to increase diuretic dose relative to those randomized to enalapril at 6, 12, 24 months post-randomization, with an overall decreased diuretic use of 2.0% (P = 0.02), 4.1% (P < 0.001), and 6.1% (P < 0.001) at 6, 12, and 24 months, respectively, with similar findings in an on-treatment analysis.

conclusionTreatment with sacubitril/valsartan was associated with more loop diuretic dose reductions and fewer dose increases compared with enalapril, suggesting that treatment with sacubitril/valsartan may reduce the requirement for loop diuretics relative to enalapril in patients with heart failure with reduced ejection fraction.

Indexed as

AminobutyratesEnalaprilFurosemideHeart FailureStroke VolumeTetrazolesAgedAngiotensin Receptor AntagonistsBiological AvailabilityBiphenyl CompoundsDose-Response Relationship, DrugDrug CombinationsDrug MonitoringFemaleHumansMaleAminobutyratesAngiotensin Receptor AntagonistsBiphenyl CompoundsDrug CombinationsEnalaprilFurosemidesacubitril and valsartan sodium hydrate drug combinationSodium Potassium Chloride Symporter InhibitorsTetrazolesValsartanDiureticsEnalaprilHeart failure with reduced ejection fractionRandomized clinical trialSacubitril/valsartan

Identifiers

PMID30741494
PMCPMC6607492
OpenAlexW2914497003

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.