Effects of omapatrilat on hemodynamics and safety in patients with heart failure

Marc Klapholz, Ignatius Thomas, Calvin Eng, Bruce J. Iteld, George A. Ponce, Alan L. Niederman, Martin S Bilsker, J. Thomas Heywood, David Synhorst

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Omapatrilat, a novel vasopeptidase inhibitor, is a highly potent and selective inhibitor of neutral endopeptidase and angiotensin-converting enzyme; its therapeutic potential is being investigated for treatment of hypertension and heart failure. In the present study, the safety, tolerability, and hemodynamic effects of single oral doses of omapatrilat (1 to 50 mg) are compared with placebo in patients with heart failure. Patients with heart failure (New York Heart Association functional class II to IV) and a resting left ventricular ejection fraction ≤40% were enrolled in a double-blind, placebo-controlled, sequential-panel study of single doses of omapatrilat of 1, 2.5, 5, 10, 25, or 50 mg, followed by hemodynamic assessment for 24 hours. At 4 to 6 hours after dosing, the 25- and 50-mg doses of omapatrilat, compared with placebo, reduced mean pulmonary capillary wedge pressure by ≈6 mm Hg from 20 and 23 mm Hg at baseline to 14 and 16 mm Hg. The 50-mg omapatrilat dose maintained this effect compared with placebo with an ≈2.5-mm Hg reduction in mean pulmonary capillary wedge pressure at 24 hours. Omapatrilat improved additional hemodynamic parameters, including cardiac index, systemic vascular resistance, stroke volume index, and mean arterial pressure. Additionally, by 2 hours after dosing with omapatrilat 25 and 50 mg, a trend in peak increases from baseline in plasma atrial natriuretic peptide (twofold) and cyclic guanosine monophosphate (nearly twofold) was observed. Moreover, omapatrilat was well tolerated. Thus, omapatrilat administered orally to patients with heart failure was safe and well tolerated and resulted in improved hemodynamic performance.

Original languageEnglish
Pages (from-to)657-661
Number of pages5
JournalAmerican Journal of Cardiology
Volume88
Issue number6
DOIs
StatePublished - Sep 15 2001
Externally publishedYes

Fingerprint

Patient Safety
Heart Failure
Hemodynamics
Placebos
Pulmonary Wedge Pressure
Stroke Volume
omapatrilat
Neprilysin
Cyclic GMP
Atrial Natriuretic Factor
Peptidyl-Dipeptidase A
Treatment Failure
Vascular Resistance
Arterial Pressure
Hypertension
Safety

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Klapholz, M., Thomas, I., Eng, C., Iteld, B. J., Ponce, G. A., Niederman, A. L., ... Synhorst, D. (2001). Effects of omapatrilat on hemodynamics and safety in patients with heart failure. American Journal of Cardiology, 88(6), 657-661. https://doi.org/10.1016/S0002-9149(01)01809-4

Effects of omapatrilat on hemodynamics and safety in patients with heart failure. / Klapholz, Marc; Thomas, Ignatius; Eng, Calvin; Iteld, Bruce J.; Ponce, George A.; Niederman, Alan L.; Bilsker, Martin S; Heywood, J. Thomas; Synhorst, David.

In: American Journal of Cardiology, Vol. 88, No. 6, 15.09.2001, p. 657-661.

Research output: Contribution to journalArticle

Klapholz, M, Thomas, I, Eng, C, Iteld, BJ, Ponce, GA, Niederman, AL, Bilsker, MS, Heywood, JT & Synhorst, D 2001, 'Effects of omapatrilat on hemodynamics and safety in patients with heart failure', American Journal of Cardiology, vol. 88, no. 6, pp. 657-661. https://doi.org/10.1016/S0002-9149(01)01809-4
Klapholz, Marc ; Thomas, Ignatius ; Eng, Calvin ; Iteld, Bruce J. ; Ponce, George A. ; Niederman, Alan L. ; Bilsker, Martin S ; Heywood, J. Thomas ; Synhorst, David. / Effects of omapatrilat on hemodynamics and safety in patients with heart failure. In: American Journal of Cardiology. 2001 ; Vol. 88, No. 6. pp. 657-661.
@article{acad20455fcf4bef858b49a572f70396,
title = "Effects of omapatrilat on hemodynamics and safety in patients with heart failure",
abstract = "Omapatrilat, a novel vasopeptidase inhibitor, is a highly potent and selective inhibitor of neutral endopeptidase and angiotensin-converting enzyme; its therapeutic potential is being investigated for treatment of hypertension and heart failure. In the present study, the safety, tolerability, and hemodynamic effects of single oral doses of omapatrilat (1 to 50 mg) are compared with placebo in patients with heart failure. Patients with heart failure (New York Heart Association functional class II to IV) and a resting left ventricular ejection fraction ≤40{\%} were enrolled in a double-blind, placebo-controlled, sequential-panel study of single doses of omapatrilat of 1, 2.5, 5, 10, 25, or 50 mg, followed by hemodynamic assessment for 24 hours. At 4 to 6 hours after dosing, the 25- and 50-mg doses of omapatrilat, compared with placebo, reduced mean pulmonary capillary wedge pressure by ≈6 mm Hg from 20 and 23 mm Hg at baseline to 14 and 16 mm Hg. The 50-mg omapatrilat dose maintained this effect compared with placebo with an ≈2.5-mm Hg reduction in mean pulmonary capillary wedge pressure at 24 hours. Omapatrilat improved additional hemodynamic parameters, including cardiac index, systemic vascular resistance, stroke volume index, and mean arterial pressure. Additionally, by 2 hours after dosing with omapatrilat 25 and 50 mg, a trend in peak increases from baseline in plasma atrial natriuretic peptide (twofold) and cyclic guanosine monophosphate (nearly twofold) was observed. Moreover, omapatrilat was well tolerated. Thus, omapatrilat administered orally to patients with heart failure was safe and well tolerated and resulted in improved hemodynamic performance.",
author = "Marc Klapholz and Ignatius Thomas and Calvin Eng and Iteld, {Bruce J.} and Ponce, {George A.} and Niederman, {Alan L.} and Bilsker, {Martin S} and Heywood, {J. Thomas} and David Synhorst",
year = "2001",
month = "9",
day = "15",
doi = "10.1016/S0002-9149(01)01809-4",
language = "English",
volume = "88",
pages = "657--661",
journal = "American Journal of Cardiology",
issn = "0002-9149",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - Effects of omapatrilat on hemodynamics and safety in patients with heart failure

AU - Klapholz, Marc

AU - Thomas, Ignatius

AU - Eng, Calvin

AU - Iteld, Bruce J.

AU - Ponce, George A.

AU - Niederman, Alan L.

AU - Bilsker, Martin S

AU - Heywood, J. Thomas

AU - Synhorst, David

PY - 2001/9/15

Y1 - 2001/9/15

N2 - Omapatrilat, a novel vasopeptidase inhibitor, is a highly potent and selective inhibitor of neutral endopeptidase and angiotensin-converting enzyme; its therapeutic potential is being investigated for treatment of hypertension and heart failure. In the present study, the safety, tolerability, and hemodynamic effects of single oral doses of omapatrilat (1 to 50 mg) are compared with placebo in patients with heart failure. Patients with heart failure (New York Heart Association functional class II to IV) and a resting left ventricular ejection fraction ≤40% were enrolled in a double-blind, placebo-controlled, sequential-panel study of single doses of omapatrilat of 1, 2.5, 5, 10, 25, or 50 mg, followed by hemodynamic assessment for 24 hours. At 4 to 6 hours after dosing, the 25- and 50-mg doses of omapatrilat, compared with placebo, reduced mean pulmonary capillary wedge pressure by ≈6 mm Hg from 20 and 23 mm Hg at baseline to 14 and 16 mm Hg. The 50-mg omapatrilat dose maintained this effect compared with placebo with an ≈2.5-mm Hg reduction in mean pulmonary capillary wedge pressure at 24 hours. Omapatrilat improved additional hemodynamic parameters, including cardiac index, systemic vascular resistance, stroke volume index, and mean arterial pressure. Additionally, by 2 hours after dosing with omapatrilat 25 and 50 mg, a trend in peak increases from baseline in plasma atrial natriuretic peptide (twofold) and cyclic guanosine monophosphate (nearly twofold) was observed. Moreover, omapatrilat was well tolerated. Thus, omapatrilat administered orally to patients with heart failure was safe and well tolerated and resulted in improved hemodynamic performance.

AB - Omapatrilat, a novel vasopeptidase inhibitor, is a highly potent and selective inhibitor of neutral endopeptidase and angiotensin-converting enzyme; its therapeutic potential is being investigated for treatment of hypertension and heart failure. In the present study, the safety, tolerability, and hemodynamic effects of single oral doses of omapatrilat (1 to 50 mg) are compared with placebo in patients with heart failure. Patients with heart failure (New York Heart Association functional class II to IV) and a resting left ventricular ejection fraction ≤40% were enrolled in a double-blind, placebo-controlled, sequential-panel study of single doses of omapatrilat of 1, 2.5, 5, 10, 25, or 50 mg, followed by hemodynamic assessment for 24 hours. At 4 to 6 hours after dosing, the 25- and 50-mg doses of omapatrilat, compared with placebo, reduced mean pulmonary capillary wedge pressure by ≈6 mm Hg from 20 and 23 mm Hg at baseline to 14 and 16 mm Hg. The 50-mg omapatrilat dose maintained this effect compared with placebo with an ≈2.5-mm Hg reduction in mean pulmonary capillary wedge pressure at 24 hours. Omapatrilat improved additional hemodynamic parameters, including cardiac index, systemic vascular resistance, stroke volume index, and mean arterial pressure. Additionally, by 2 hours after dosing with omapatrilat 25 and 50 mg, a trend in peak increases from baseline in plasma atrial natriuretic peptide (twofold) and cyclic guanosine monophosphate (nearly twofold) was observed. Moreover, omapatrilat was well tolerated. Thus, omapatrilat administered orally to patients with heart failure was safe and well tolerated and resulted in improved hemodynamic performance.

UR - http://www.scopus.com/inward/record.url?scp=0035885017&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035885017&partnerID=8YFLogxK

U2 - 10.1016/S0002-9149(01)01809-4

DO - 10.1016/S0002-9149(01)01809-4

M3 - Article

C2 - 11564390

AN - SCOPUS:0035885017

VL - 88

SP - 657

EP - 661

JO - American Journal of Cardiology

JF - American Journal of Cardiology

SN - 0002-9149

IS - 6

ER -