Natriuretic peptides serve as both critical biomarkers for diagnosing heart failure and therapeutic targets, with the combination drug sacubitril/valsartan being the only successful clinical strategy to harness their protective effects.
Only 1 successful strategyOf all natriuretic peptide therapeutic approaches, only sacubitril/valsartan (combined NEP/ARB inhibition) reduced cardiovascular mortality in clinical trials
What the researchers found
This review traces the evolution of natriuretic peptides from basic biology to clinical application. ANP and BNP are released by the heart during overload and act as natural counterweights to the renin-angiotensin-aldosterone system — lowering blood pressure, reducing fluid retention, and inhibiting harmful cardiac remodeling.
BNP and its precursor fragment NT-proBNP have become established diagnostic and prognostic biomarkers for heart failure. However, the body's natriuretic peptide response during heart failure is insufficient to prevent disease progression. Of various therapeutic strategies attempted — including synthetic peptide analogs and inhibition of the enzyme that degrades natriuretic peptides (NEP) — only the combined NEP inhibitor/angiotensin receptor blocker sacubitril/valsartan demonstrated clinical success in reducing cardiovascular mortality and morbidity.
Why it matters
Heart failure affects over 60 million people worldwide. Natriuretic peptides represent one of the most successful peptide-to-medicine stories: the same molecules used for diagnosis (BNP blood tests) also became therapeutic targets. The success of sacubitril/valsartan — which works by preventing natriuretic peptide breakdown — fundamentally changed heart failure treatment guidelines and demonstrated that augmenting endogenous peptide systems can save lives.
How the study worked
This is a narrative review article synthesizing published research on natriuretic peptide biology, their role as biomarkers, and therapeutic strategies targeting the natriuretic peptide system. It covers basic science, clinical diagnostics, and drug development outcomes.
What this study cannot tell us
As a narrative review, this paper summarizes existing literature rather than presenting new data. It reflects the state of knowledge as of 2018, so more recent developments in natriuretic peptide therapeutics are not covered. The review focuses primarily on heart failure, with less coverage of natriuretic peptide roles in other conditions like kidney disease or metabolic syndrome.
How to read the evidence
This is a narrative review article that synthesizes prior research rather than reporting original data. It provides a useful overview of the field but carries the inherent limitations of expert opinion and selective literature review.
When this study was published
Published in 2018, this review captures the landscape shortly after sacubitril/valsartan's landmark PARADIGM-HF trial. The core concepts remain accurate, though newer data on natriuretic peptide-guided therapy and additional indications have since emerged.
The bigger picture
Natriuretic peptides illustrate a broader pattern in peptide medicine: endogenous peptides that the body produces for self-regulation can become both diagnostic tools and therapeutic targets. The sacubitril/valsartan success story — blocking the enzyme that degrades these peptides rather than administering them directly — has influenced drug development strategies across peptide therapeutics, including approaches to other cardiovascular, renal, and metabolic conditions.
Questions still open
- Could next-generation natriuretic peptide analogs with longer half-lives succeed where earlier synthetic versions failed?
- How do natriuretic peptide levels and therapeutic responses differ across patient populations, including by age, sex, and obesity status?
Common questions
What are natriuretic peptides and why does the heart release them?
Why did most natriuretic peptide drugs fail while sacubitril/valsartan succeeded?
Read the original research
Evolving Role of Natriuretic Peptides from Diagnostic Tool to Therapeutic Modality.
Advances in experimental medicine and biology, 1067, 109-131
Citation
Pagel-Langenickel, Ines. (2018). Evolving Role of Natriuretic Peptides from Diagnostic Tool to Therapeutic Modality.. Advances in experimental medicine and biology, 1067, 109-131. https://doi.org/10.1007/5584_2018_143