Omapatrilat Reduces Pulse Pressure and Proximal Aortic Stiffness in Patients with Systolic Hypertension. Results of the Conduit Hemodynamics of Omipatrilat International Research Study - Omapatrilat

Description:

The goal of this study was to assess the safety and efficacy of omapatrilat, a vasopeptidase with both ACE and neutral endopeptidase inhibitor activity, on vascular stiffness in patients with predominantly systolic hypertension.

Study Design

Study Design:

Mean Follow Up: 12 weeks

Patient Populations:

SBP greater than 160mm Hg but less than 200mm Hg and diastolic BP less than 110 mm Hg

Exclusions:

intolerance to at least 40 mg of omapatrilat or 20 mg of enalapril, CHF and peripheral vascular disease

Drug/Procedures Used:

A 12-week double-blind randomized clinical trial comparing monotherapy and omapatrilat 80mg daily (n=87) to 40mg of enalapril (n=80) in patients with predominantly systolic hypertension. Eligible patients had a SBP greater than 160mm Hg but less than 200mm Hg and diastolic BP less than 110 mm Hg following a 1-2 week placebo lead in. Exclusions included intolerance to at least 40 mg of omapatrilant or 20 mg of enalapril, CHF and peripheral vascular disease. Pulse wave velocity (PWV) was obtained by multisite arterial tonometry with an ECG reference and aortic compliance/stiffness using pulse volumes and echo-Doppler derived stroke volumes.

Principal Findings:

There was no difference between groups regarding age (mean 61 years), male gender (62%), CAD (3-5%), smokers (12%), use of lipid lowering drugs (25%) or percent of women taking estrogens (39%). The omapatrilant group had 13% with diabetes compared to 5% on enalapril, p 0.066. There was no difference between groups in baseline BP [163/85(117)mm Hg], mean flow rate, peripheral resistance, central stiffness, carotid-radial PWV or carotid-femoral PWV. After 12 weeks, compared to enalapril, the omapatrilat group had a lower SBP, dBP, pulse pressure, mean pressure, borderline lower PWV, improved waveform morphology with a decrease in reflectance wave and significantly reduced Zc, a measure of central aortic stiffness.

Interpretation:

Among patients with systolic hypertension, greater reductions in pulse pressure and central aortic stiffness treated with omapatrilat compared with enalapril suggest that aortic stiffness is maintained by specific, partially reversible mechanisms, and underscore a potential for drug modulation of natriuretic peptides in treatment of hypertension.

References:

Mitchell GF, Izzo JL, Lacourciere Y, et al. Omapatrilat Reduces Pulse Pressure and Proximal Aortic Stiffness in Patients with Systolic Hypertension. Results of the Conduit Hemodynamics of Omipatrilat International Research Study. Circulation 2002; 105:2955-61.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Hypertension

Keywords: Enalapril, Pulse Wave Analysis, Pyridines, Protease Inhibitors, Electrocardiography, Peripheral Vascular Diseases, Vascular Stiffness, Natriuretic Peptides, Manometry, Estrogens, Thiazepines, Stroke Volume, Vascular Resistance, Hypertension, Diabetes Mellitus


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