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

Pulse pressure has recently emerged as a strong independent predictor of cardiovascular events in the general population and in essential hypertension (EH). Therefore, pulse pressure reduction may represent an important new therapeutic goal in EH. Basic research suggests a favorable effect of natriuretic peptides on conduit vessels. Therefore, we assessed changes in peripheral (PPP) and central (CPP) pulse pressure and conduit vessel stiffness in a 12-week double blind, randomized clinical trial that compared the monotherapeutic effects of angiotensin converting enzyme (ACE) inhibition with enalapril (N=87) versus vasopeptidase (dual ACE plus neutral endopeptidase) inhibition with omapatrilat (N=80). Patients were withdrawn from standard antihypertensive medication for 1-2 weeks prior to enrollment and systolic pressure was confirmed to be ≥160 mmHg. Using calibrated tonometry and pulsed Doppler, pulsatile hemodynamics were assessed prior to randomization and 24 hours after last dose of study medication. Omapatrilat produced greater reductions in PPP, CPP and characteristic impedance (Zc), which is a direct measure of the stiffness of the central aorta. The differential change in Zc remained significant (P < 0.05) after adjusting for baseline Zc, baseline mean pressure and change in mean pressure. Vasopeptidase inhibition with omapatrilat, as compared to converting enzyme inhibition with enalapril, produced greater reductions in peripheral and central pulse pressure in association with a pressure-independent reduction in proximal aortic stiffness (Zc). These findings are consistent with a favorable effect of natriuretic peptides on central conduit vessel function. (See Table) P = difference between treatments P = difference between treatments