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Impact of estimated total blood volume on NT-proBNP response to angiotensin receptor-neprilysin inhibition in acute heart failure: Insights from the PREMIER study.

Kazutaka Nogi·Atsushi Tanaka·Takumi Imai·Shunichi Doi·Kohei Kamishita·Hideki Kawai·Masaru Obokata·Keisuke Kida·Yuya Matsue·Hideo Izawa·Shungo Hikoso·Koichi Node·PREMIER Study Investigators
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Abstract

BACKGROUND: Sacubitril/valsartan (Sac/Val) reduces N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in acute heart failure (AHF), particularly in patients with reduced ejection fraction. However, whether estimated total blood volume (TBV), calculated using anthropometric equations, is associated with heterogeneity in biomarker response remains uncertain. METHODS: This post hoc exploratory sub-analysis of the PREMIER randomized trial evaluated whether baseline estimated TBV was associated with heterogeneity in NT-proBNP reduction after Sac/Val compared with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) therapy. Estimated TBV was calculated using validated anthropometric equations and dichotomized at the median (4.05 L). Patients were further stratified by left ventricular ejection fraction (LVEF <40% vs &#x2265;40%). The primary endpoint was the proportional change in NT-proBNP from baseline to Week 8. RESULTS: Among 376 patients, 372 with baseline estimated TBV data were analyzed. In the high TBV group, Sac/Val was associated with greater NT-proBNP reduction than ACEI/ARB (-56% vs -32%; ratio of change, 0.67; 95% confidence interval, 0.53-0.84; P = .001), whereas no significant difference was observed in the low TBV group (P for heterogeneity = 0.063). In patients with LVEF <40%, Sac/Val was associated with greater NT-proBNP reduction in both TBV groups. In patients with LVEF &#x2265;40%, Sac/Val was associated with greater NT-proBNP reduction in the high TBV group, whereas the point estimate in the low TBV group numerically favored ACEI/ARB. CONCLUSIONS: In this exploratory post hoc analysis, higher estimated TBV was associated with greater NT-proBNP reduction after Sac/Val, particularly among patients with LVEF &#x2265;40%. These findings are hypothesis-generating and require external validation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05164653; Japan Registry of Clinical Trials, jRCTs021210046.

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HumansHeart FailureFemalePeptide FragmentsMaleNatriuretic Peptide, BrainBiphenyl CompoundsAgedNeprilysinValsartanAngiotensin Receptor AntagonistsStroke VolumeAminobutyratesTetrazolesDrug CombinationsBlood VolumeAcute DiseaseAngiotensin-Converting Enzyme InhibitorsBiomarkersMiddle AgedTreatment OutcomeJournal ArticleRandomized Controlled TrialMulticenter Study

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Kazutaka Nogi, Atsushi Tanaka, Takumi Imai, Shunichi Doi, Kohei Kamishita, Hideki Kawai, Masaru Obokata, Keisuke Kida, Yuya Matsue, Hideo Izawa, Shungo Hikoso, Koichi Node, PREMIER Study Investigators. 2026-08-01. Impact of estimated total blood volume on NT-proBNP response to angiotensin receptor-neprilysin inhibition in acute heart failure: Insights from the PREMIER study.. https://doi.org/10.1016/j.ahj.2026.107549

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Journal Article; Randomized Controlled Trial; Multicenter Study resourceAcute Disease subjectAged subjectAminobutyrates subjectAngiotensin Receptor Antagonists subjectAngiotensin-Converting Enzyme Inhibitors subjectBiomarkers subjectBiphenyl Compounds subjectBlood Volume subjectDrug Combinations subjectFemale subjectHeart Failure subjectHumans subjectJournal Article subjectMale subjectMiddle Aged subject

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