Changes in Natriuretic Peptide Levels and Cardiac Structure in Patients Treated With Vericiguat

Q: What are the key findings of this study?

High-dose vericiguat was independently associated with a significantly greater reduction in log-transformed NT-proBNP at 3 months compared to low-dose vericiguat (β=-0.125), but not with cardiac reverse remodeling.

Q: What is the clinical evidence from this study?

Study design: Observational. Population: Heart failure with reduced ejection fraction (HFrEF) (n=504). Intervention: High-dose vericiguat (7.5 or 10 mg) vs. Low-dose vericiguat (≤5 mg). Primary outcome: Change in log-transformed NT-proBNP at 3 months (β=-0.125, 95% CI -0.247, -0.004, p=0.043).

Kenji Kanenawa; Kenji Ando; Takahito Nasu; Wataru Fujimoto; N Kagiyama; Yasuyuki Shiraishi; Shunsuke Ishii; Takeshi Ijichi; Gaku Nakazawa; Koshiro Kanaoka; Shingo Matsumoto; VERIFY-HF Investigators

doi:10.1253/circj.cj-25-1087

March 26, 2026Circulation JournalOpen Access

Changes in Natriuretic Peptide Levels and Cardiac Structure in Patients Treated With Vericiguat

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Key result

High-dose vericiguat is linked to greater NT-proBNP reduction vs low-dose, without improving cardiac remodeling.

β=-0.125
95% CI -0.247, -0.004
P=0.043
n=504

Why the study?

Changes in NT-proBNP levels and cardiac remodeling from baseline to follow-up in patients with HFrEF treated with vericiguat remain unclear.

Does high-dose vericiguat improve NT-proBNP levels and cardiac remodeling compared to low-dose vericiguat in patients with HFrEF?

Key Points

To examine changes in NT-proBNP levels and cardiac remodeling from baseline to follow-up in patients with heart failure with reduced ejection fraction treated with vericiguat.
Conducted a real-world registry study of patients with heart failure with reduced ejection fraction receiving vericiguat titrated up to high doses (7.5 mg or 10 mg) versus low doses (≤5 mg).
Evaluated NT-proBNP reductions using least-squares geometric mean ratios and assessed cardiac remodeling via echocardiographic changes (LVEF, LVEDVI, LVESVI) up to 12 months.
Performed multivariable linear regression to assess the association of vericiguat dose and background guideline-directed medical therapy with biomarker and structural changes.
High-dose vericiguat demonstrated significantly greater NT-proBNP reduction at 3 months compared with low-dose vericiguat (least-squares geometric mean ratio 0.53 [95% CI 0.46–0.61] vs. 0.65 [95% CI 0.59–0.72], P=0.009; multivariable β=−0.131, 95% CI −0.257 to −0.006, P=0.041).
By 12 months, the association between vericiguat dose and NT-proBNP was no longer significant between low- and high-dose groups (geometric mean 0.51 [95% CI 0.46–0.57] vs. 0.49 [95% CI 0.43–0.55], P=0.52).

Study Design

Type

Observational (n=504)

Multicenter

Yes

Structured PICO

Does high-dose vericiguat improve NT-proBNP levels and cardiac remodeling compared to low-dose vericiguat in patients with HFrEF?

P

Population

504 adult patients with heart failure with reduced ejection fraction newly prescribed vericiguat, followed for 12 months.

E

Exposure

High-dose vericiguat (7.5 or 10 mg) added to guideline-directed medical therapy.

C

Comparator

Low-dose vericiguat (<5 mg) added to guideline-directed medical therapy.

O

Outcome

Change in log-transformed NT-proBNP from baseline to follow-up (primarily at 3 months) and changes in cardiac remodeling (echocardiographic parameters) at 12 months.surrogate

Main Result

Mean Difference: -0.125 (95% CI -0.247–-0.004)

p-value: p=0.043

In a real-world registry of HFrEF patients, vericiguat dose-dependently reduced NT-proBNP levels but did not significantly drive cardiac reverse remodeling.

Limitations

Survival bias due to exclusion of patients who died or were lost to follow-up before 6 months
Lack of a control group not treated with vericiguat
Potential underreporting or misclassification of events in electronic medical records
Effects of subsequent treatments initiated after baseline were not assessed
Limited generalizability outside of Japan

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Implication

High-dose vericiguat may lower NT-proBNP in real-world HFrEF; hypothesis-generating for remodeling effects and requires RCT confirmation.

Abstract

BACKGROUND: Changes in N-terminal pro B-type natriuretic peptide (NT-proBNP) levels and cardiac remodeling from baseline to follow-up in patients with heart failure with reduced ejection fraction (HFrEF) treated with vericiguat remain unclear. METHODS AND RESULTS: ) and was predominantly associated with newly initiated β-blockers or renin-angiotensin system inhibitors within 3 months prior to vericiguat administration or prior heart failure hospitalization rather than vericiguat dose. CONCLUSIONS: In this real-world registry study, high-dose vericiguat was associated with sustained dose-dependent reductions in NT-proBNP, but not cardiac reverse remodeling.

Cite This Study

Kanenawa et al. (2026) conducted an observational in Heart failure with reduced ejection fraction (HFrEF) (n=504). High-dose vericiguat (7.5 or 10 mg) vs. Low-dose vericiguat (≤5 mg) was evaluated on Change in log-transformed NT-proBNP at 3 months (β=-0.125, 95% CI -0.247, -0.004, p=0.043). High-dose vericiguat was independently associated with a significantly greater reduction in log-transformed NT-proBNP at 3 months compared to low-dose vericiguat (β=-0.125), but not with cardiac reverse remodeling.

synapsesocial.com/papers/69c8c15ade0f0f753b39bc24 https://doi.org/10.1253/circj.cj-25-1087

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Changes in Natriuretic Peptide Levels and Cardiac Structure in Patients Treated With Vericiguat

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Discussion

Implication

Abstract

Cite This Study

Changes in Natriuretic Peptide Levels and Cardiac Structure in Patients Treated With Vericiguat

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Discussion

Implication

Abstract

Cite This Study

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