Vasopeptidase Inhibitor Omapatrilat Versus ACE Inhibitor: Similar Neurohormone Effects in Heart Failure
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.
Quick Facts
What This Study 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.
Key Numbers
How They Did This
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.
Why This Research Matters
Direct comparison shows vasopeptidase inhibition provides all ACE inhibitor benefits plus additional natriuretic peptide modulation — supporting the dual-inhibition concept despite clinical limitations.
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.
What This Study Doesn't Tell Us
Omapatrilat was subsequently limited by angioedema risk. The NP reduction mechanism (improved function vs degradation) could not be definitively determined.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- ACE benefits + more Omapatrilat provided all lisinopril's neurohormonal benefits PLUS additional natriuretic peptide reduction — supporting the concept that became Entresto
- Evidence Grade:
- Moderate evidence from a randomized comparison with comprehensive neurohormonal profiling in heart failure.
- Study Age:
- Published in 2002. Omapatrilat was not approved due to angioedema, but the concept evolved into sacubitril/valsartan (Entresto), which achieved landmark clinical success.
- Original Title:
- Comparison of the effects of omapatrilat and lisinopril on circulating neurohormones and cytokines in patients with chronic heart failure.
- Published In:
- The American journal of cardiology, 90(5), 496-500 (2002)
- Authors:
- Sheth, Tej, Parker, Tom, Block, Alan, Hall, Christian, Adam, Albert, Pfeffer, Mark A, Stewart, Duncan J, Qian, Chunlin, Rouleau, Jean L
- Database ID:
- RPEP-00769
Evidence Hierarchy
Frequently Asked 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 More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-00769APA
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.
MLA
Sheth, Tej, et al. "Comparison of the effects of omapatrilat and lisinopril on circulating neurohormones and cytokines in patients with chronic heart failure.." The American journal of cardiology, 2002.
RethinkPeptides
RethinkPeptides Research Database. "Comparison of the effects of omapatrilat and lisinopril on c..." RPEP-00769. Retrieved from https://rethinkpeptides.com/research/sheth-2002-comparison-of-the-effects
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.