Boosting Natriuretic Peptides With Sacubitril/Valsartan May Benefit Heart Failure Patients on Dialysis | Research

The takeaway

A review of clinical evidence finds sacubitril/valsartan — which works by boosting natriuretic peptide levels — improved heart function and reduced mortality in end-stage kidney disease patients with heart failure, with an acceptable safety profile.

Improved LVEF and reduced mortality in ESRD
Sacubitril/valsartan's dual mechanism — blocking RAAS while boosting natriuretic peptides — provides benefits in dialysis patients without increasing hyperkalemia or hypotension

What the researchers found

The review of clinical evidence for sacubitril/valsartan in ESRD patients with heart failure found:

Benefits (particularly in patients with reduced ejection fraction):

- Improved ventricular remodeling (reversed harmful heart enlargement)

- Enhanced left ventricular ejection fraction (better heart pumping)

- Reduced mortality rates

- Reduced heart failure rehospitalization rates

Safety:

- No significant increased risk of hyperkalemia (high potassium — a major concern in dialysis patients)

- No significant increased risk of hypotension

- Favorable overall safety profile

Mechanism: Sacubitril/valsartan simultaneously regulates the RAAS (renin-angiotensin-aldosterone system) and enhances natriuretic peptide signaling, providing dual cardiovascular protection.

Why it matters

Dialysis patients have a cardiovascular mortality rate 10-30 times higher than the general population. Heart failure is the leading cause of death in this group, yet they've been largely excluded from the major heart failure trials that established sacubitril/valsartan's benefits. The mechanism is particularly relevant for these patients: by inhibiting neprilysin, sacubitril preserves natriuretic peptides (BNP and ANP) that help the body excrete salt and water and protect the heart — functions critically needed in patients whose kidneys can no longer perform these roles.

How the study worked

Comprehensive literature review searching PubMed, Embase, and Web of Science through December 2024 for clinical evidence on sacubitril/valsartan use in ESRD patients. The review covers pharmacological mechanisms, pharmacokinetics, and clinical outcomes data from available studies in this population, along with discussion of challenges and future directions.

What this study cannot tell us

This is a narrative review, not a systematic review or meta-analysis. The available evidence in ESRD patients is limited — most sacubitril/valsartan trials excluded severe kidney disease. The studies reviewed are mostly small, observational, and heterogeneous. The drug's impact on residual kidney function in dialysis patients needs further study. Dialysis timing relative to drug dosing affects pharmacokinetics and wasn't standardized across studies.

How to read the evidence

This is a narrative review synthesizing limited clinical evidence. While sacubitril/valsartan has robust evidence from large trials in the general heart failure population (PARADIGM-HF), the evidence specific to ESRD is mostly from small, observational studies. The review provides a useful clinical summary but cannot provide high-certainty conclusions for this specific population.

When this study was published

Published in 2025, this review captures the most current evidence through December 2024 for a clinical question that is increasingly relevant as nephrologists and cardiologists seek to improve outcomes in dialysis patients with heart failure.

The bigger picture

Sacubitril/valsartan represents a paradigm shift in heart failure treatment: rather than just blocking harmful systems (RAAS), it simultaneously enhances protective ones (natriuretic peptides). Natriuretic peptides — BNP and ANP — are among the body's most important cardiovascular protective peptides. In ESRD patients who lack kidney function, boosting these peptide pathways may be even more important because the kidneys can no longer contribute to fluid and sodium homeostasis. This review extends the peptide-based cardiovascular protection story to one of medicine's highest-risk populations.

Questions still open

Should sacubitril/valsartan be started proactively in ESRD patients before heart failure develops as a preventive strategy?
How should dosing be adjusted for dialysis patients, and should doses be timed around dialysis sessions?
Will a large randomized trial specifically in ESRD patients confirm the benefits suggested by smaller studies?

Common questions

How does sacubitril/valsartan work through natriuretic peptides?

The body produces natriuretic peptides (BNP and ANP) when the heart is stressed. These peptides help by relaxing blood vessels, reducing fluid retention, and protecting the heart. Normally, an enzyme called neprilysin breaks these beneficial peptides down. Sacubitril blocks neprilysin, allowing natriuretic peptide levels to stay higher and continue their protective effects. Combined with valsartan (which blocks the harmful angiotensin pathway), the drug provides dual cardiovascular protection.

Why is this drug particularly relevant for dialysis patients?

Dialysis patients have extremely high rates of heart failure because their kidneys can no longer regulate fluid and blood pressure effectively. Boosting natriuretic peptides — which help excrete salt and water and protect the heart — is especially valuable when the kidneys aren't working. Additionally, the safety data showing no increased hyperkalemia risk is reassuring, since high potassium is already a major concern in dialysis patients and has been a barrier to using this drug in this population.

Read the original research

Efficacy and safety of sacubitril/valsartan in end-stage renal disease patients with heart failure: a review.

Annals of medicine, 57(1), 2557515

View on PubMed ↗Publisher’s paper ↗

Citation

Li, Peiyun; Li, Yupei; Zhang, Ling. (2025). Efficacy and safety of sacubitril/valsartan in end-stage renal disease patients with heart failure: a review.. Annals of medicine, 57(1), 2557515. https://doi.org/10.1080/07853890.2025.2557515