Prognostic Implications of N-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin T in EMPEROR-Preserved.

N-terminal pro–B-type natriuretic peptide (NT-proBNP) empagliflozin heart failure high-sensitivity cardiac troponin (hs-cTn) prognosis

Journal

JACC. Heart failure
ISSN: 2213-1787
Titre abrégé: JACC Heart Fail
Pays: United States
ID NLM: 101598241

Informations de publication

Date de publication:
07 2022
Historique:
received: 06 05 2022
accepted: 17 05 2022
pubmed: 8 6 2022
medline: 6 7 2022
entrez: 7 6 2022
Statut: ppublish

Résumé

N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are associated with disease severity and outcomes among patients with heart failure (HF) with preserved ejection fraction. The authors evaluated associations between both biomarkers and clinical outcomes in the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction) trial. Of 5,988 study participants, 5,986 (99.9%) and 5,825 (97.3%) had available baseline NT-proBNP and hs-cTnT; postbaseline NT-proBNP was also available. Baseline characteristics were expressed by biomarker quartiles. The effect of empagliflozin on cardiovascular death/ HF hospitalization, the individual components, total HF hospitalizations, slope of decline of estimated glomerular filtration rate (eGFR), and a composite renal endpoint were examined across biomarker quartiles. Change in NT-proBNP across study visits as a function of treatment assignment was also assessed. Higher baseline NT-proBNP and hs-cTnT concentrations were associated with more comorbidities and worse HF severity. Incidence rates for cardiac and renal outcomes were 2- to 5-fold higher among those in the highest vs lowest NT-proBNP or hs-cTnT quartiles. Empagliflozin consistently reduced the risk for cardiovascular events and reduced slope of eGFR decline across NT-proBNP or hs-cTnT quartiles. Empagliflozin treatment modestly lowered NT-proBNP; by 100 weeks, the adjusted mean difference in NT-proBNP from placebo was 7%. Increase in NT-proBNP from baseline to 12 weeks was strongly associated with risk of cardiovascular death/HF hospitalization. The benefit of empagliflozin on cardiac outcomes and decline of eGFR is preserved across the wide range of baseline NT-proBNP and hs-cTnT evaluated. Empagliflozin modestly reduces NT-proBNP in HF with preserved ejection fraction. (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction [EMPEROR-Preserved]; NCT03057951).

Sections du résumé

BACKGROUND
N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are associated with disease severity and outcomes among patients with heart failure (HF) with preserved ejection fraction.
OBJECTIVES
The authors evaluated associations between both biomarkers and clinical outcomes in the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction) trial.
METHODS
Of 5,988 study participants, 5,986 (99.9%) and 5,825 (97.3%) had available baseline NT-proBNP and hs-cTnT; postbaseline NT-proBNP was also available. Baseline characteristics were expressed by biomarker quartiles. The effect of empagliflozin on cardiovascular death/ HF hospitalization, the individual components, total HF hospitalizations, slope of decline of estimated glomerular filtration rate (eGFR), and a composite renal endpoint were examined across biomarker quartiles. Change in NT-proBNP across study visits as a function of treatment assignment was also assessed.
RESULTS
Higher baseline NT-proBNP and hs-cTnT concentrations were associated with more comorbidities and worse HF severity. Incidence rates for cardiac and renal outcomes were 2- to 5-fold higher among those in the highest vs lowest NT-proBNP or hs-cTnT quartiles. Empagliflozin consistently reduced the risk for cardiovascular events and reduced slope of eGFR decline across NT-proBNP or hs-cTnT quartiles. Empagliflozin treatment modestly lowered NT-proBNP; by 100 weeks, the adjusted mean difference in NT-proBNP from placebo was 7%. Increase in NT-proBNP from baseline to 12 weeks was strongly associated with risk of cardiovascular death/HF hospitalization.
CONCLUSIONS
The benefit of empagliflozin on cardiac outcomes and decline of eGFR is preserved across the wide range of baseline NT-proBNP and hs-cTnT evaluated. Empagliflozin modestly reduces NT-proBNP in HF with preserved ejection fraction. (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction [EMPEROR-Preserved]; NCT03057951).

Identifiants

pubmed: 35670067
pii: S2213-1779(22)00302-X
doi: 10.1016/j.jchf.2022.05.004
pii:
doi:

Substances chimiques

Biomarkers 0
Peptide Fragments 0
Troponin T 0
pro-brain natriuretic peptide (1-76) 0
Natriuretic Peptide, Brain 114471-18-0

Banques de données

ClinicalTrials.gov
['NCT03057951']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

512-524

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Funding Support and Author Disclosures The EMPEROR-Reduced trial was supported by Boehringer Ingelheim and Eli Lilly and Company. Dr Januzzi is supported in part by the Hutter Family Professorship at Harvard Medical School; is a Trustee of the American College of Cardiology; is a Board member of Imbria Pharmaceuticals; has received grant support from Applied Therapeutics, Innolife, Novartis Pharmaceuticals, and Abbott Diagnostics; has received consulting income from Abbott, Janssen, Novartis, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Amgen, Bayer, CVRx, Janssen, MyoKardia and Takeda. Dr Butler has received consulting income from Abbott, Adrenomed, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Roche, and Vifor. Dr Zannad has received steering committee personal fees from Acceleron, Applied Therapeutics, Bayer, Boehringer, CVRx, Novartis, Merck, MSD; has received consultancy personal fees from Cardior, Cereno, Cellprothera, Owkin, NovoNordisk, Servier, Vifor Fresenius; has stock options at Cereno Pharmaceutical, Cardior, and G3Pharmaceutical; and is the founder of Cardiorenal and CVCT. Dr Filippatos has received lectures and/or committee member contributions in trials sponsored by Medtronic, Vifor, Servier, Novartis, Bayer, Amgen, and Boehringer Ingelheim. Drs Ferreira and Pocock are consultants for Boehringer Ingelheim. Dr Sattar has consulted for Amgen, AstraZeneca, Boehringer Ingelheim, Eli-Lilly, Hanmi Pharmaceuticals, Novo Nordisk, Novartis, Novartis, Sanofi, and Pfizer; and has received grant support from Boehringer Ingelheim. Dr Verma has received research and/or speaker honoraria from Amgen, Amarin, AstraZeneca, Bayer, CMS, Janssen, HLS, Sanofi, Novo Nordisk, Novartis, Merck, and PhaseBio; is the president of the Canadian Medical and Surgical Knowledge Translation Research Group; and holds the Tier 1 Canada Research Chair in Cardiovascular Surgery. Drs Vedin and Brueckmann and Ms Iwata are employees of Boehringer Ingelheim. Dr Packer has received income from Actavis, Altimmune, Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Imara, Lilly, Moderna, Novartis, Reata, Relypsa, and Salamandra. Dr Anker has received fees from Abbott, Bayer, Boehringer Ingelheim, Cardiac Dimension, Cordio, Impulse Dynamics, Novartis, Occlutech, Servier, and Vifor Pharma; and has received grant support from Abbott and Vifor Pharma.

Auteurs

James L Januzzi (JL)

Cardiology Division, Massachusetts General Hospital, Harvard Medical School, and Baim Institute for Clinical Research, Boston, Massachusetts, USA. Electronic address: jjanuzzi@partners.org.

Javed Butler (J)

Department of Medicine, University of Mississippi School of Medicine, Jackson, Mississippi, USA.

Faiez Zannad (F)

Université de Lorraine, Inserm INI-CRCT, CHRU, Nancy, France.

Gerasimos Filippatos (G)

National and Kapodistrian University of Athens School of Medicine, Athens University Hospital Attikon, Athens, Greece.

João Pedro Ferreira (JP)

Université de Lorraine, Inserm, Centre d'Investigation Clinique Plurithématique, CHRU de Nancy, Nancy, France; UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal.

Stuart J Pocock (SJ)

Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Naveed Sattar (N)

BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.

Subodh Verma (S)

Division of Cardiac Surgery, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada.

Ola Vedin (O)

Boehringer-Ingelheim AB, Stockholm, Sweden.

Tomoko Iwata (T)

Boehringer Ingelheim Pharma GmbH and Co KG, Biberach, Germany.

Martina Brueckmann (M)

Boehringer Ingelheim International GmbH, Ingelheim, Germany; First Department of Medicine, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.

Milton Packer (M)

Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, Texas, USA; Imperial College, London, United Kingdom.

Stefan D Anker (SD)

Department of Cardiology (CVK), and the Berlin Institute of Health Center for Regenerative Therapies, German Centre for Cardiovascular Research Partner Site Berlin, Charité Universitätsmedizin, Berlin, Germany.

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Classifications MeSH