The safety and 24-hour antihypertensive efficacy of the vasopeptidase inhibitor Omapatrilat: a pilot study

Ruddy, Michael C.; Guthrie, Robert; Papademetriou, V.; Moulton, Kristen; Saini, R.P.

doi:10.1016/s0895-7061(99)80440-3

Cited by 15 publications

(10 citation statements)

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“…In patients with mild to moderate hypertension, omapatrilat produced dose-dependent decreases in ambulatory blood pressure over 24 hours [37,38]. Thus, concomitant with what the pharmacodynamic biomarkers indicated, the antihypertensive effects of omapatrilat are long-lasting and support once-daily dosing in clinical use [39].…”

Section: Omapatrilat For Hypertension and Congestive Heart Failurementioning

confidence: 93%

Effects of omapatrilat on pharmacodynamic biomarkers of neutral endopeptidase and angiotensin-converting enzyme activity in humans

Vesterqvist

Reeves

2001

Current Science Inc

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Vasopeptidase inhibition is a new concept in blood pressure management. A single molecule simultaneously inhibits two enzymes that regulate cardiovascular function: neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE)[1]. Development of vasopeptidase inhibitors stemmed from the need for new and more efficacious antihypertensive agents that not only reduce blood pressure but also treat hypertension as part of a larger syndrome involving endothelial dysfunction [2]. By inhibiting NEP and ACE, vasopeptidase inhibitors enhance the natriuretic peptide and kallikrein-kinin systems and inhibit the renin-angiotensin-aldosterone system. This article outlines the pharmacodynamic effects of the vasopeptidase inhibitor omapatrilat on biomarkers of NEP and ACE activity in humans.

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Section: Omapatrilat For Hypertension and Congestive Heart Failurementioning

confidence: 93%

Effects of omapatrilat on pharmacodynamic biomarkers of neutral endopeptidase and angiotensin-converting enzyme activity in humans

Vesterqvist

Reeves

2001

Current Science Inc

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“…The drops in systolic blood pressure averaged 15 to 25 mm Hg, and the decreases in diastolic blood pressure were between 9 and 16 mm Hg. The peak-to-trough ratios were approximately 61% to 78%, supporting once-daily dosing [50,51]. Using a different VPI, MDL 100240, Rousso et al [52] have further found that both urinary flow rate and sodium excretion increased, along with a drop in blood pressure, in healthy volunteers, demonstrating the potential diuretic effect of this class of drugs.…”

Section: Vasopeptidase Inhibitors In Hypertensionmentioning

confidence: 93%

“…Several randomized studies reported that omapatrilat caused statistically significant, dose-dependent decreases in both diastolic and systolic blood pressure [49,50]. The drops in systolic blood pressure averaged 15 to 25 mm Hg, and the decreases in diastolic blood pressure were between 9 and 16 mm Hg.…”

Section: Vasopeptidase Inhibitors In Hypertensionmentioning

confidence: 99%

Vasopeptidase inhibition: A new direction in cardiovascular treatment

Asher

Naftilan

2000

Current Science Inc

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The development of new antihypertensive agents is becoming even more important. We need better blood pressure control and also agents that treat hypertension as a disease of the vascular endothelium. Recently, it has been shown that blocking the renin-angiotensin system with angiotensin converting enzyme (ACE) inhibitors reduces blood pressure and decreases the incidence of vascular disease. Another peptide system, the natriuretic peptide system, has also been shown to be important in blood pressure control and volume homeostasis. Because ACE and neutral endopeptidase, the enzyme responsible for the degradation of the natriuretic peptides, are both zinc metalloproteases, new pharmaceuticals that inhibit both enzymes have been developed. The first of these, omapatrilat, has been shown to be an effective antihypertensive agent and to have great potential for treating congestive heart failure.

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“…48 Human data established that omapatrilat is an effective antihypertensive in a wide variety of clinical settings. [49][50] The drug significantly reduces blood pressure across the wide spectrum of hypertensive patients including AfricanAmericans, the elderly, and salt-sensitive individuals. It exerts favorable effects in animal models of heart failure, and preliminary evidence suggests beneficial effects in patients with heart failure due to systolic dysfunction.…”

Section: Smentioning

confidence: 99%

The Role of the Renin‐Angiotensin‐Aldosterone System in the Management of Heart Failure

Rodgers

Patterson

2000

Pharmacotherapy

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Numerous clinical trials have highlighted the role of the renin‐angiotensin‐aldosterone (RAA) system in the development and progression of heart failure. Over 30 randomized, controlled trials have evaluated the effects of angiotensin‐converting enzyme (ACE) inhibitors on morbidity and mortality in over 7000 patients with heart failure. Cumulative evidence from these trials shows that these agents significantly reduce mortality and hospitalizations, slow disease progression, and improve exercise tolerance and New York Heart Association class. The Heart Failure Society of America guidelines recommend ACE inhibitors as standard therapy for patients with left ventricular systolic dysfunction. The angiotensin receptor blockers and spironolactone offer alternative and perhaps complimentary mechanisms by which the RAA system may be therapeutically manipulated. The role of these therapies in treating heart failure is discussed.

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The safety and 24-hour antihypertensive efficacy of the vasopeptidase inhibitor Omapatrilat: a pilot study

Cited by 15 publications

References 0 publications

Effects of omapatrilat on pharmacodynamic biomarkers of neutral endopeptidase and angiotensin-converting enzyme activity in humans

Effects of omapatrilat on pharmacodynamic biomarkers of neutral endopeptidase and angiotensin-converting enzyme activity in humans

Vasopeptidase inhibition: A new direction in cardiovascular treatment

The Role of the Renin‐Angiotensin‐Aldosterone System in the Management of Heart Failure

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