Emerging treatments for hypertension: potential role for vasopeptidase inhibition

Hypertension remains uncontrolled worldwide despite the availability of several classes of antihypertensive agents. There is an increased risk of serious cardiovascular, cerebrovascular, and renal events if the disease goes untreated or is poorly treated. Thus, the high incidence of hypertension coupled with its poor control make it imperative that more effective and well-tolerated treatments that exhibit target-organ protection be developed. Vasopeptidase inhibitors are a new class of cardiovascular agents that simultaneously inhibit neutral endopeptidase and angiotensin converting enzyme. They enhance peptides with vasodilatory and possibly organ-protective properties and also inhibit the production of the vasoconstrictor angiotensin II. In preclinical studies, omapatrilat has shown blood pressure-lowering effects independent of renin status and has increased survival in an animal model of congestive heart failure. Human studies with omapatrilat, the most clinically advanced vasopeptidase inhibitor, administered orally once daily have demonstrated powerful dose-dependent reduction of systolic and diastolic blood pressures, regardless of age, race, or gender. Omapatrilat is particularly effective in lowering systolic blood pressure; this article summarizes data from recent clinical trials. This drug is well tolerated, with adverse effects comparable to those of currently available antihypertensive agents. Omapatrilat and other vasopeptidase inhibitors have potential applications in the treatment of hypertension, heart failure, and other cardiac and vascular disorders.