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Stroke Volume / Angiotensin-converting Enzyme Inhibitors / Biomarkers · Journal article
American Heart Journal · August 1, 2026
Raises a question worth testing. It does not answer one.
This post hoc exploratory analysis of the PREMIER trial found that sacubitril/valsartan achieved greater NT-proBNP reduction than ACEI/ARB in patients with high estimated total blood volume (≥4.05 L), with a ratio of change of 0.67 (95% CI 0.53–0.84, P=0.001), but the difference was not statistically significant in the low TBV group (P for heterogeneity 0.063). The authors acknowledge this is hypothesis-generating and requires external validation.
Post hoc exploratory subgroup analysis of a randomized controlled trial. 372 patients from the PREMIER trial with baseline estimated total blood volume data; enrolled with acute heart failure diagnosis.. Intervention: Sacubitril/valsartan (Sac/Val). Compared with: Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB). n = 372. Not stated in source text..
In high TBV group: Sac/Val achieved −56% NT-proBNP reduction versus −32% with ACEI/ARB (ratio of change 0.67; 95% CI 0.53–0.84; P=0.001) In low TBV group: no significant difference observed between Sac/Val and ACEI/ARB (P for heterogeneity = 0.063) In LVEF <40%: Sac/Val associated with greater NT-proBNP reduction in both TBV groups
NT-proBNP is a biomarker; no clinical hard endpoints (mortality, rehospitalization, symptom relief) reported.
These findings suggest that estimated total blood volume may identify a subgroup (high TBV, particularly those with LVEF ≥40%) in whom sacubitril/valsartan achieves superior NT-proBNP reduction compared to ACEI/ARB. However, the hypothesis-generating nature and need for external validation means these results should not yet guide clinical practice or patient selection.
Post hoc exploratory subanalysis of a parent RCT using a calculated variable (estimated total blood volume) to interrogate heterogeneity in a biomarker endpoint; the authors explicitly state findings are hypothesis-generating and require external validation.
As stated by the source record.
Quoted from the source exactly as published.
These findings suggest that estimated total blood volume may identify a subgroup (high TBV, particularly those with LVEF ≥40%) in whom sacubitril/valsartan achieves superior NT-proBNP reduction compared to ACEI/ARB. However, the hypothesis-generating nature and need for external validation means these results should not yet guide clinical practice or patient selection.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
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 ≥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 ≥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 ≥40%. These findings are hypothesis-generating and require external validation.Trial registration. ClinicalTrials.gov, NCT05164653; Japan Registry of Clinical Trials, jRCTs021210046.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.