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(Hypertension. 2001;38:1342.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Omapatrilat Versus Lisinopril

Efficacy and Neurohormonal Profile in Salt-Sensitive Hypertensive Patients

Vito M. Campese; Kenneth C. Lasseter; Carlos M. Ferrario; William B. Smith; Michael C. Ruddy; Clarence E. Grim; Ronald D. Smith; Ramon Vargas; Michael F. Habashy; Ole Vesterqvist; Carol L. Delaney; Wei-Chi Liao

From Keck School of Medicine, University of Southern California (V.M.C., M.F.H.), Los Angeles; Clinical Pharmacology Associates (K.C.L.), Miami, Fla; Bowman Gray School of Medicine (C.M.F.), Winston-Salem, NC; New Orleans Center for Clinical Research (W.B.S., R.V.), La; UMDNJ–Robert Wood Johnson Medical School (M.C.R.), New Brunswick, NJ; Medical College of Wisconsin (C.E.G.), Milwaukee; Wake Forest University (R.D.S.), Winston-Salem, NC; Bristol-Myers Squibb Pharmaceutical Research Institute (O.V., C.L.D.), Princeton, NJ; and Covance Inc (W.-C.L.), Princeton, NJ.

Correspondence to Vito M. Campese, MD, Professor of Medicine and Chief Division of Nephrology, Keck School of Medicine, University Southern California Medical Center, 1200 N State St, Los Angeles, CA 90033. E-mail campese{at}hsc.usc.edu

Omapatrilat, a vasopeptidase inhibitor, simultaneously inhibits neutral endopeptidase and ACE. The efficacy and hormonal profile of omapatrilat and lisinopril were compared in salt-sensitive hypertensive patients. On enrollment, antihypertensive medications were withdrawn, and patients received a single-blind placebo. On day 15, salt-sensitivity determinations were made. Salt-sensitive hypertensive patients returned within 5 to 10 days for baseline evaluations of ambulatory diastolic blood pressure, ambulatory systolic blood pressure, and atrial natriuretic peptide. Salt-sensitive hypertensive patients were randomized to receive double-blind omapatrilat (n=28) or lisinopril (n=33) at initial doses of 10 mg for 1 week, increasing to 40 and 20 mg, respectively, for an additional 3 weeks. Ambulatory blood pressure and urinary atrial natriuretic peptide were assessed at study termination. Both omapatrilat and lisinopril significantly reduced mean 24-hour ambulatory diastolic and systolic blood pressures; however, omapatrilat produced significantly greater reductions in mean 24-hour ambulatory diastolic blood pressure (P=0.008), ambulatory systolic blood pressure (P=0.004), and ambulatory mean arterial pressure (P=0.005) compared with values from lisinopril. Both drugs potently inhibited ACE over 24 hours. Omapatrilat significantly (P<0.001) increased urinary excretion of atrial natriuretic peptide over 0- to 24-hour (3.8-fold) and 12- to 24-hour (2-fold) intervals; lisinopril produced no change. Omapatrilat significantly (P<0.001) increased urinary excretion of cGMP over the 0- to 24- and 4- to 8-hour intervals compared with that from lisinopril. Neither drug had a diuretic, natriuretic, or kaliuretic effect. In conclusion, in salt-sensitive hypertensive patients, omapatrilat demonstrated the hormonal profile of a vasopeptidase inhibitor and lowered ambulatory diastolic and systolic blood pressures more than lisinopril.

Key Words: omapatrilat • lisinopril • vasopeptidase inhibitor • salt sensitivity

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