Vasopeptidase Inhibitor Omapatrilat Versus ACE Inhibitor: Similar Neurohormone Effects in Heart Failure | Research

The takeaway

Omapatrilat (vasopeptidase inhibitor) and lisinopril (ACE inhibitor) had similar effects on neurohormones and inflammatory cytokines in heart failure patients, with omapatrilat also lowering natriuretic peptide levels — suggesting additional benefit.

ACE benefits + more
Omapatrilat provided all lisinopril's neurohormonal benefits PLUS additional natriuretic peptide reduction — supporting the concept that became Entresto

What the researchers found

Omapatrilat and lisinopril had equivalent effects on angiotensin II, aldosterone, and inflammatory cytokines in CHF, but omapatrilat additionally reduced natriuretic peptide levels, suggesting superior cardiac functional improvement.

Why it matters

Direct comparison shows vasopeptidase inhibition provides all ACE inhibitor benefits plus additional natriuretic peptide modulation — supporting the dual-inhibition concept despite clinical limitations.

How the study worked

Randomized controlled trial comparing omapatrilat versus lisinopril in chronic heart failure patients. Neurohormones (ANP, BNP, angiotensin II, aldosterone, endothelin), inflammatory cytokines (TNF-α, IL-6), and hemodynamics measured.

What this study cannot tell us

Omapatrilat was subsequently limited by angioedema risk. The NP reduction mechanism (improved function vs degradation) could not be definitively determined.

How to read the evidence

Moderate evidence from a randomized comparison with comprehensive neurohormonal profiling in heart failure.

When this study was published

Published in 2002. Omapatrilat was not approved due to angioedema, but the concept evolved into sacubitril/valsartan (Entresto), which achieved landmark clinical success.

The bigger picture

This head-to-head comparison validated the vasopeptidase concept that later evolved into sacubitril/valsartan (Entresto). The neurohormonal similarity plus NP difference supported the rationale for dual inhibition.

Questions still open

Does the additional NP effect translate to clinical outcome benefit?
Why didn't omapatrilat achieve approval despite promising neurohormonal data?
Does sacubitril/valsartan show the same neurohormonal profile?

Common questions

Was omapatrilat better than ACE inhibitors?

The neurohormonal data said yes — it had all the ACE inhibitor benefits plus additional natriuretic peptide modulation. But clinical development was halted by angioedema risk, leading to the refined approach in Entresto.

Is this related to Entresto?

Yes. Omapatrilat proved the concept of dual inhibition but had safety issues. Entresto achieves the same dual benefit (neprilysin + RAAS inhibition) with a safer design, and is now a standard heart failure treatment.

Read the original research

Comparison of the effects of omapatrilat and lisinopril on circulating neurohormones and cytokines in patients with chronic heart failure.

The American journal of cardiology, 90(5), 496-500

View on PubMed ↗

Citation

Sheth, Tej; Parker, Tom; Block, Alan; Hall, Christian; Adam, Albert; Pfeffer, Mark A; Stewart, Duncan J; Qian, Chunlin; Rouleau, Jean L. (2002). Comparison of the effects of omapatrilat and lisinopril on circulating neurohormones and cytokines in patients with chronic heart failure.. The American journal of cardiology, 90(5), 496-500.