Evidence map›Paper›PMID 33459776›Full record

Trial reportEuropean heart journal2021

Influence of neprilysin inhibition on the efficacy and safety of empagliflozin in patients with chronic heart failure and a reduced ejection fraction: the EMPEROR-Reduced trial.

Milton Packer, Stefan D Anker, Javed Butler, Gerasimos Filippatos, Joao Pedro Ferreira, Stuart J Pocock, Hans-Peter Brunner-La Rocca, Stefan Janssens, Hiroyuki Tsutsui, Jian Zhang and 7 more

Open access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in European heart journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 4 pooled it
15.6field-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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 4 syntheses or guidelines pooled it, 133 citations in OpenAlex.

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  14. Updates on New Therapies for Patients with CKD.Kidney international reports · 2024
    Review
  15. Sodium-glucose co-transporter 2 inhibitors in heart failure: an updated evidence-based practical guidance for clinicians.European heart journal supplements : journal of the European Society of Cardiology · 2023
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 12 institutions in 10 countries.

Milton PackerBaylor Heart and Vascular Institute, Baylor University Medical Center, 621 N. Hall Street, Dallas, TX, USA.
Stefan D AnkerDepartment of Cardiology (CVK), and Berlin Institute of Health Center for Regenerative Therapies, German Centre for Cardiovascular Research Partner Site Berlin, Charité Universitätsmedizin, Berlin, Germany.
Javed ButlerDepartment of Medicine, University of Mississippi School of Medicine, Jackson, MS, USA.
Gerasimos FilippatosNational and Kapodistrian, University of Athens School of Medicine, Athens University Hospital Attikon, Athens, Greece.
Joao Pedro FerreiraUniversité de Lorraine, Inserm INI-CRCT, CHRU, Nancy, France.
Stuart J PocockDepartment of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
Hans-Peter Brunner-La RoccaDepartment of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands.
Stefan JanssensDepartment of Cardiology, University Hospital Gasthuisberg of Leuven, Leuven, Belgium.
Hiroyuki TsutsuiDepartment of Cardiovascular Medicine, Kyushu University, Higashi-ku, Fukuoka, Japan.
Jian ZhangFuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Martina BrueckmannBoehringer Ingelheim International GmbH and Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
Waheed JamalBoehringer Ingelheim International GmbH, Ingelheim, Germany.
Daniel CottonBoehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA.
Tomoko IwataBoehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
Janet SchneeBoehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA.
Faiez ZannadUniversité de Lorraine, Inserm INI-CRCT, CHRU, Nancy, France.
EMPEROR-Reduced Trial Committees and Investigators
Boehringer Ingelheim (Germany) · DEInserm · FRAcademy of Medical Sciences · GBBaylor University Medical Center · USBoehringer Ingelheim (Taiwan) · TWBoehringer Ingelheim (United States) · USGerman Centre for Cardiovascular Research · DEKyushu University · JPLondon School of Hygiene & Tropical Medicine · GBNational and Kapodistrian University of Athens · GRUniversity Medical Center · USUniversity of Mississippi Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsWe evaluated the influence of sacubitril/valsartan on the effects of sodium-glucose cotransporter 2 (SGLT2) inhibition with empagliflozin in patients with heart failure and a reduced ejection fraction. METHODS AND

resultsThe EMPEROR-Reduced trial randomized 3730 patients with heart failure and an ejection fraction ≤40% to placebo or empagliflozin (10 mg/day), in addition to recommended treatment for heart failure, for a median of 16 months. A total of 727 patients (19.5%) received sacubitril/valsartan at baseline. Analysis of the effect of neprilysin inhibition was 1 of 12 pre-specified subgroups. Patients receiving a neprilysin inhibitor were particularly well-treated, as evidenced by lower systolic pressures, heart rates, N-terminal prohormone B-type natriuretic peptide, and greater use of cardiac devices (all P < 0.001) when compared with those not receiving sacubitril/valsartan. Nevertheless, when compared with placebo, empagliflozin reduced the risk of cardiovascular death or hospitalization for heart failure in patients receiving or not receiving sacubitril/valsartan [hazard ratio 0.64 (95% CI 0.45-0.89), P = 0.009 and hazard ratio 0.77 (95% CI 0.66-0.90), P = 0.0008, respectively, interaction P = 0.31]. Empagliflozin slowed the rate of decline in estimated glomerular filtration rate by 1.92 ± 0.80 mL/min/1.73 m2/year in patients taking a neprilysin inhibitor (P = 0.016) and by 1.71 ± 0.35 mL/min/1.73 m2/year in patients not taking a neprilysin inhibitor (P < 0.0001), interaction P = 0.81. Combined inhibition of SGLT2 and neprilysin was well-tolerated.

conclusionThe effects on empagliflozin to reduce the risk of heart failure and renal events are not diminished in intensively treated patients who are receiving sacubitril/valsartan. Combined treatment with both SGLT2 and neprilysin inhibitors can be expected to yield substantial additional benefits.

Indexed as

Heart FailureNeprilysinAminobutyratesAngiotensin Receptor AntagonistsBenzhydryl CompoundsDrug CombinationsGlucosidesHumansStroke VolumeTetrazolesAminobutyratesAngiotensin Receptor AntagonistsBenzhydryl CompoundsDrug CombinationsempagliflozinGlucosidesNeprilysinTetrazolesEmpagliflozinHeart failureSacubitril/valsartan

Identifiers

PMID33459776
PMCPMC7878011
OpenAlexW3124689165

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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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.