Neutral Endopeptidase Blocker Promising In Heart Failure

NEW YORK (Reuters Health) - A neutral endopeptidase (NEP) inhibitor with endothelin-converting enzyme (ECE) inhibitory properties is effective in reducing pulmonary pressure in patients with congestive heart failure.

In the July 15th issue of the American Journal of Cardiology, Dr. Kenneth Dickstein of the University of Bergen in Stavanger, Norway, and colleagues note that, while NEP inhibitors have been shown to raise natriuretic peptide levels, there is a simultaneous rise in endothelin-1 that limits the biologic effects.

The researchers conducted a double-blind trial of the dual NEP/ECE inhibitor, SLV306, in 75 heart failure patients who underwent right-sided heart catheterization. They were randomized to treatment with a single 200, 400 or 800 mg dose of the agent or to placebo.

Pulmonary pressures and right atrial pressures decreased significantly in all the active treatment groups, but there were "virtually no changes" in the placebo group.

The maximum decrease in pressure took place from 6 to 8 hours after medication administration, but there was no clear dose-related response.

The agent was well tolerated and appeared to have no significant effects on heart rate, systemic blood pressure or cardiac output.

It did, however, increase plasma natriuretic peptide and big endothelin 1 levels, confirming, say the investigators, its inhibition of NEP and ECE. This combination of effects, the team concludes, "may be useful in heart failure by reducing left and right cardiac filling pressures."

Source: Am J Cardiol 2004;94:237-239. [ Google search on this article ]

MeSH Headings: Biological Factors : Immunologic and Biological Factors : Peptide Hydrolases : Endopeptidases : Pulmonary Wedge Pressure : Endothelins : Endothelin-1 : Chemical Actions and Uses : Chemical Actions : Chemicals and Drugs