Elsevier

JACC: Heart Failure

Volume 10, Issue 9, September 2022, Pages 677-688
JACC: Heart Failure

Clinical Research
Sequential Evaluation of NT-proBNP in Heart Failure: Insights Into Clinical Outcomes and Efficacy of Vericiguat

https://doi.org/10.1016/j.jchf.2022.04.015Get rights and content
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Abstract

Background

The effect of vericiguat on sequential N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels and influence of this relationship on clinical outcomes is unknown.

Objectives

This study assessed the relationship between changes in NT-proBNP and the primary outcome (cardiovascular death or heart failure hospitalization); evaluated the effect of vericiguat on changes in NT-proBNP; and explored the association between the efficacy of vericiguat and changes in NT-proBNP.

Methods

NT-proBNP was measured at randomization and at 16, 32, 48, and 96 weeks in 4,805 of 5,050 patients. The association between NT-proBNP change at week 16 and the primary outcome was assessed. The relationship between changes in NT-proBNP and the primary outcome according to treatment group was assessed by using joint modeling and mediation analysis.

Results

A significant and sustained decline in NT-proBNP levels was seen in both treatment groups. After week 16, NT-proBNP levels decreased more with vericiguat vs placebo (any reduction: odds ratio [OR]: 1.45 [95% CI: 1.28-1.65]; P < 0.001; ≥50% reduction: OR: 1.27 [95% CI: 1.10-1.47]; P = 0.001) and were less likely to increase (≥20% increase: OR: 0.68 [95% CI: 0.59-0.78]; P < 0.001; ≥50% increase: OR: 0.70 [95% CI: 0.59-0.82]; P < 0.001). The treatment effect related to serial NT-proBNP on the primary composite outcome was HR: 0.96 (95% CI: 0.95-0.99) at week 16, which increased to HR: 0.90 (95% CI: 0.85-0.96) at week 48; the average extent of mediation of the composite outcome related to NT-proBNP was 45%.

Conclusions

In patients with worsening HFrEF, vericiguat significantly decreased NT-proBNP levels compared with placebo. This change appeared associated with a modest relative improvement in the primary outcome of cardiovascular death or heart failure hospitalization. (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction [VICTORIA]; NCT02861534)

Key Words

heart failure
natriuretic peptide
N-terminal pro-B-type natriuretic peptide (NT-proBNP)
vericiguat

Abbreviations and Acronyms

HF
heart failure
HFrEF
heart failure with reduced ejection fraction
NT-proBNP
N-terminal pro–B-type natriuretic peptide
OR
odds ratio
SGLT2
sodium-glucose cotransporter-2

Cited by (0)

John Teerlink, MD, served as the Guest Editor for this paper.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.