ArticleJournal of the American Heart Association2024
Phosphodiesterase 9 Inhibition Combined With Valsartan and With Sacubitril/Valsartan in Experimental Ovine Heart Failure.
Article in Journal of the American Heart Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
- Case Report: Generalized anxiety disorder and hypertension: a bidirectional loop unraveled by integrated management.Frontiers in psychiatry · 2025Article
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLCZ696 (sacubitril/valsartan) antagonizes the renin-angiotensin system while simultaneously augmenting the natriuretic peptides (NPs). Inhibition of phosphodiesterase 9 inhibition (PDE9i), which hydrolyses NP-generated cGMP may be a more specific means of enhancing NP bioactivity. The objective of the present study was to compare for the first time effects of LCZ696 and PDE9i+valsartan in experimental heart failure (HF) and investigate combination PDE9i+LCZ696. METHODS AND
resultsSeven sheep received, on separate days, intravenous boli of (1) LCZ696, (2) PDE9i+valsartan, (3) PDE9i+LCZ696, and (4) vehicle control, during mild HF and severe HF. Compared with control, LCZ696 and PDE9i+LCZ696 induced similar increases in plasma NPs (greater increments in severe HF), whereas PDE9i+valsartan reduced NP levels. Circulating cGMP was elevated following LCZ696 and PDE9i+valsartan, and further increased with combination PDE9i+LCZ696. All active treatments increased plasma renin and angiotensin II (greater increments in severe HF). Plasma aldosterone was unchanged. Plasma endothelin-1 was elevated by LCZ696 and PDE9i+LCZ696, but not PDE9i+valsartan. Active treatments reduced arterial and left atrial pressure and peripheral resistance and increased cardiac output (more pronounced in severe-HF). PDE9i+LCZ696 induced greater hemodynamic changes relative to LCZ696 and PDE9i+valsartan. Treatments had minimal renal effect in mild HF. In severe HF, treatments elevated urine cGMP in association with significant increases in creatinine clearance and diuresis and natriuresis, effects especially prominent with PDE9i+LCZ696.
conclusionsLCZ696 and PDE9i+valsartan have similar beneficial hemodynamic and renal effects in HF, with combined PDE9i+LCZ696 producing additional improvements. Overall, effects were significantly greater in severe HF. Findings suggest PDE9i might serve as a replacement for neprilysin inhibition or as an adjunct therapy to LCZ696.
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