Dr James L Januzzi
Cardiologist, Massachusetts General Hospital. Prof of Medicine, Harvard Medical School

Impact of ARNi Therapy on Natriuretic Peptide Use


  • BNP is a substrate of Neprilysin degardation hence it's interpretation becomes more challenging in patinets on ARNi
  • NT-proBNP is not degraded by Neprilysin and will most likely become the gold standard biomarker for the measurement in patients taking ARNi

The PARADIGM-HF trial recently demonstrated a 20% reduction in heart failure hospitalisation, 20% reduction in cardiovascular death, and a 16% reduction in all-cause mortality related to the use of an ARNi. This was in comparison to Enalapril, the gold standard for heart failure management. So, given these results, it’s very reasonable to expect that therapy with an ARNi will become the new gold standard for heart failure management.

One of the vasoactive peptides that rises in patients taking an ARNi is BNP. So, as a consequence, when a patient is treated with this class of drugs, their BNP values rise. In theory, this is a benefit for the patient. We don’t really know if the BNP rise explains the benefit of the drug. It’s probably a combination of multiple peptides, rather than just BNP. But what is clear is that interpretation of BNP becomes much more challenging when a patient is taking an ARNi, because the degree of rise in their BNP value is somewhat variable from patient to patient.

In contrast, NT-proBNP, which is not degraded by Neprilysin, does not rise when patients are treated with an ARNi, and, in fact, NT-proBNP typically rapidly falls after the initiation of the drug, reflecting the benefit of the drug. And NT-proBNP will likely become the gold standard biomarker for measurement in patients taking the drug.

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