Omapatrilat reduces pulse pressure and proximal aortic stiffness in patients with systolic hypertension: Results of the conduit hemodynamics of omapatrilat international research study

• Published in: Circulation (New York, N.Y.) Vol. 105; no. 25; pp. 2955 - 2961
• Main Authors: MITCHELL, Gary F, IZZO, Joseph L, LACOURCIERE, Yves, OUELLET, Jean-Pascal, NEUTEL, Joel, CHUNLIN QIAN, KERWIN, Linda J, BLOCK, Alan J, PFEFFER, Marc A
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 25-06-2002
• Subjects: Adult; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Antihypertensive agents; Antihypertensive Agents - therapeutic use; Aorta - drug effects; Aorta - physiopathology; Biological and medical sciences; Blood Pressure - drug effects; Cardiovascular system; Double-Blind Method; Enalapril - therapeutic use; Female; Hemodynamics - drug effects; Humans; Hypertension - drug therapy; Hypertension - physiopathology; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Protease Inhibitors - therapeutic use; Pyridines - therapeutic use; Systole; Thiazepines - therapeutic use; Human; Systolic hypertension; Enzyme; Treatment efficiency; Pulse; Enzyme inhibitor; Cardiovascular disease; Exploration; Compliance(volume pressure); Peptidases; Chemotherapy; Treatment; Enalapril; Omapatrilat; Antihypertensive agent; Hydrolases; Aorta; Blood pressure; Stiffness; Hemodynamics; ACE inhibitor; Comparative study
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000020500.77568.3C

Increased pulse pressure, an indicator of conduit vessel stiffness, is a strong independent predictor of cardiovascular events in hypertensive cohorts, which suggests that reduction of conduit vessel stiffness may be desirable in hypertension.
We assessed changes in pulse pressure and conduit vessel stiffness in a 12-week double-blind, randomized clinical trial that compared monotherapy with the ACE inhibitor enalapril 40 mg daily (n=87) versus the vasopeptidase (dual ACE and neutral endopeptidase) inhibitor omapatrilat 80 mg daily (n=80) in patients with systolic hypertension. Patients were withdrawn from antihypertensive medications 1 to 2 weeks before enrollment, and systolic pressure was confirmed to be > or =160 mm Hg. With the use of calibrated tonometry and pulsed Doppler, pulsatile hemodynamics were assessed before randomization and at 12 weeks. Characteristic impedance (Z(c)), a direct measure of the stiffness of the central aorta, was calculated from the ratio of changes in carotid pressure and aortic flow in early systole. Omapatrilat compared with enalapril produced greater reductions in peripheral (-8.2+/-12.2 versus -4.0+/-12.2 mm Hg, P<0.05) and central (-10.2+/-16.2 versus -3.2+/-16.9 mm Hg, P<0.01) pulse pressures and Z(c) (237+/-83 to 208+/-70 versus 225+/-87 to 231+/-94 dyne x s/cm(5), P<0.001); the latter remained significant (P<0.05) after adjusting for change in mean pressure.
Greater reductions in pulse pressure and Z(c) in hypertensive subjects treated with omapatrilat compared with enalapril suggest that aortic stiffness is maintained by specific, partially reversible mechanisms and underscore a potential role for pharmacological modulation of natriuretic peptides in the treatment of hypertension.