Changes in mid-regional pro-adrenomedullin during treatment with sacubitril/valsartan.
Humans
Heart Failure
/ diagnostic imaging
Adrenomedullin
Neprilysin
Microcirculation
Tetrazoles
/ therapeutic use
Angiotensin Receptor Antagonists
/ therapeutic use
Stroke Volume
/ physiology
Valsartan
/ therapeutic use
Aminobutyrates
/ therapeutic use
Biphenyl Compounds
/ therapeutic use
Drug Combinations
Angiotensin receptor-neprilysin inhibitors
Biomarker
MR-proADM
Neprilysin
Sacubitril/valsartan
Journal
European journal of heart failure
ISSN: 1879-0844
Titre abrégé: Eur J Heart Fail
Pays: England
ID NLM: 100887595
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
revised:
26
05
2023
received:
22
03
2023
accepted:
23
06
2023
medline:
31
8
2023
pubmed:
4
7
2023
entrez:
4
7
2023
Statut:
ppublish
Résumé
Adrenomedullin is a vasodilatory peptide with a role in microcirculatory and endothelial homeostasis. Adrenomedullin is a substrate for neprilysin and may therefore play a role in beneficial effects of sacubitril/valsartan (Sac/Val) treatment. Mid-regional pro-adrenomedullin (MR-proADM) was measured in 156 patients with heart failure with reduced ejection fraction (HFrEF) treated with Sac/Val and 264 patients with heart failure with preserved ejection fraction (HFpEF) randomized to treatment with Sac/Val or valsartan. Echocardiography and Kansas City Cardiomyopathy Questionnaire results were collected at baseline and after 6 and 12 months in the HFrEF cohort. Median (Q1-Q3) baseline MR-proADM concentrations were 0.80 (0.59-0.99) nmol/L in HFrEF and 0.88 (0.68-1.20) nmol/L in HFpEF. After 12 weeks of treatment with Sac/Val, MR-proADM increased by median 49% in HFrEF and 60% in HFpEF, while there were no significant changes in valsartan-treated patients (median 2%). Greater increases in MR-proADM were associated with higher Sac/Val doses. Changes in MR-proADM correlated weakly with changes in N-terminal pro-B-type natriuretic peptide, cardiac troponin T and urinary cyclic guanosine monophosphate. Increases in MR-proADM were associated with decreases in blood pressure, but not significantly associated with changes in echocardiographic parameters or health status. MR-proAD concentrations rise substantially following treatment with Sac/Val, in contrast to no change from valsartan. Change in MR-proADM from neprilysin inhibition did not correlate with improvements in cardiac structure and function or health status. More data are needed regarding the role of adrenomedullin and its related peptides in the treatment of heart failure. PROVE-HF ClinicalTrials.gov Identifier: NCT02887183, PARAMOUNT ClinicalTrials.gov Identifier: NCT00887588.
Substances chimiques
sacubitril
17ERJ0MKGI
Adrenomedullin
148498-78-6
Neprilysin
EC 3.4.24.11
Tetrazoles
0
Angiotensin Receptor Antagonists
0
Valsartan
80M03YXJ7I
Aminobutyrates
0
Biphenyl Compounds
0
Drug Combinations
0
Banques de données
ClinicalTrials.gov
['NCT00887588', 'NCT02887183']
Types de publication
Randomized Controlled Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1396-1405Informations de copyright
© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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