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


RESULTS
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 Patients were withdrawn from antihypertensive medications 1 to 2 weeks before enrollment, and systolic pressure was confirmed to be 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.


CONCLUSIONS
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.
Mitchell
Gary F
GF
Cardiovascular Engineering, Inc, Holliston, Mass 01746, USA. GaryFMitchell@mindspring.com
Izzo
Joseph L
JL
Lacourcière
Yves
Y
Ouellet
Jean-Pascal
JP
Neutel
Joel
J
Qian
Chunlin
C
Kerwin
Linda J
LJ
Block
Alan J
AJ
Pfeffer
Marc A
MA
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004656:Enalapril / Q000627:therapeutic use; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D013599:Systole; D013841:Thiazepines / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D011480:Protease Inhibitors; D011725:Pyridines; D013841:Thiazepines; C106266:omapatrilat; D004656:Enalapril