Evidence map›Paper›PMID 31093657›Full record

Trial reportEuropean heart journal2019

Cardiovascular biomarkers in patients with acute decompensated heart failure randomized to sacubitril-valsartan or enalapril in the PIONEER-HF trial.

David A Morrow, Eric J Velazquez, Adam D DeVore, Margaret F Prescott, Carol I Duffy, Yared Gurmu, Kevin McCague, Ricardo Rocha, Eugene Braunwald

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

Trial report in European heart journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02554890 (A Multicenter, Randomized, Double-blind, Double Dummy, Parallel Group, Active-controlled 8-week Study to Evaluate the Effect of Sacubitril/Valsartan), which is not on this map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
8.9field-weighted citation impact, top 2% 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.

NCT02554890 phase4completednot on this map

A Multicenter, Randomized, Double-blind, Double Dummy, Parallel Group, Active-controlled 8-week Study to Evaluate the Effect of Sacubitril/Valsartan (LCZ696) Versus Enalapril on Changes in NT-proBNP and Safety and Tolerability of In-hospital Initiation of LCZ696 Compared to Enalapril in HFrEF Patients Who Have Been Stabilized Following Hospitalization for Acute Decompensated Heart Failure (ADHF).

TypeinterventionalSponsorNovartis PharmaceuticalsRan2016 to 2018Enrolled887ConditionsAcute Heart FailureArmssacubitril/valsartan (LCZ696), Enalapril, sacubitril/valsartan (LCZ696) matching placebo, enalapril matching placebo
3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 74 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Inflammation in heart failure: pathophysiology and therapeutic strategies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024
    Review
  9. Article
  10. Prognostic Value of sST2 in Heart Failure.Journal of clinical medicine · 2023
    Review
  11. Article
  12. Review
  13. Article
  14. Observational
  15. Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

David A MorrowTIMI Study Group, 75 Francis Street, Boston, MA, USA.
Eric J VelazquezDepartment of Internal Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8056, USA.
Adam D DeVoreDuke Clinical Research Institute, Duke University, 2400 Pratt St, Durham, NC, USA.
Margaret F PrescottNovartis Pharmaceuticals Corporation, 1 Health Plaza, East Hanover, NJ, USA.
Carol I DuffyNovartis Pharmaceuticals Corporation, 1 Health Plaza, East Hanover, NJ, USA.
Yared GurmuTIMI Study Group, 75 Francis Street, Boston, MA, USA.
Kevin McCagueNovartis Pharmaceuticals Corporation, 1 Health Plaza, East Hanover, NJ, USA.
Ricardo RochaNovartis Pharmaceuticals Corporation, 1 Health Plaza, East Hanover, NJ, USA.
Eugene BraunwaldTIMI Study Group, 75 Francis Street, Boston, MA, USA.
Brigham and Women's Hospital · USDuke University · USYale University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsCirculating high-sensitivity cardiac troponin (hsTn) and soluble ST2 (sST2) reflect myocardial stress in patients with heart failure (HF). Production of cyclic guanosine 3'5' monophosphate (cGMP) in response to activation of natriuretic peptide receptors reduces cardiac afterload and preload. We assessed the effects of sacubitril/valsartan on these biomarkers in patients with reduced ejection fraction and acute decompensated HF (ADHF). METHODS AND

resultsPIONEER-HF was a randomized, double-blind trial of sacubitril/valsartan vs. enalapril in hospitalized patients with ADHF following haemodynamic stabilization. We measured circulating hsTnT, sST2, and urinary cGMP at baseline, 1, 2 (sST2, cGMP), 4, and 8 weeks (n = 694 with all baseline biomarkers). Ratios of geometric means (timepoint/baseline) were determined and compared as a ratio for sacubitril/valsartan vs. enalapril. Compared with enalapril, sacubitril/valsartan led to a significantly greater decline in hsTnT and sST2. This effect emerged as early as 1 week for sST2 and was significant for both at 4 weeks with a 16% greater reduction in hsTnT (P < 0.001) and 9% greater reduction in sST2 (P = 0.0033). Serial urinary cGMP increased with sacubitril/valsartan compared with enalapril (P < 0.001, 1 week). The significant differences between treatment groups for each biomarker were sustained at 8 weeks. In an exploratory multivariable-adjusted analysis of cardiovascular death or HF-rehospitalization, the concentrations of hsTnT, sST2 at week 1 were significantly associated with subsequent outcome.

conclusionBiomarkers of myocardial stress are elevated in patients with ADHF and associated with outcome. Compared with enalapril, sacubitril/valsartan reduces myocardial injury and haemodynamic stress as reflected by biomarkers, with an onset that is apparent within 1-4 weeks. CLINICAL TRIALS REGISTRATION: NCT02554890 clinical.trials.gov.

Indexed as

Heart FailureAgedAminobutyratesAngiotensin Receptor AntagonistsBiomarkersBiphenyl CompoundsCyclic GMPDrug CombinationsEnalaprilFemaleHemodynamicsHumansInterleukin-1 Receptor-Like 1 ProteinMaleMiddle AgedTetrazolesAminobutyratesAngiotensin Receptor AntagonistsBiomarkersBiphenyl CompoundsCyclic GMPDrug CombinationsEnalaprilIL1RL1 protein, humanInterleukin-1 Receptor-Like 1 Proteinsacubitril and valsartan sodium hydrate drug combinationTetrazolesTroponinValsartanAcute heart failureBiomarkersTroponin

Identifiers

PMID31093657
PMCPMC6801941
OpenAlexW2945543541

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.