title: Omapatrilat versus lisinopril: efficacy and neurohormonal profile in salt-sensitive hypertensive patients.
abstract: 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 On enrollment, antihypertensive medications were withdrawn, and patients received a single-blind placebo.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.
authors.affiliation: Keck School of Medicine, University of Southern California, Los Angeles 90033, USA. campese@hsc.usc.edu
authors.forename: V M
authors.initials: VM
authors.lastname: Campese
authors.forename: K C
authors.initials: KC
authors.lastname: Lasseter
authors.forename: C M
authors.initials: CM
authors.lastname: Ferrario
authors.forename: W B
authors.initials: WB
authors.lastname: Smith
authors.forename: M C
authors.initials: MC
authors.lastname: Ruddy
authors.forename: C E
authors.initials: CE
authors.lastname: Grim
authors.forename: R D
authors.initials: RD
authors.lastname: Smith
authors.forename: R
authors.initials: R
authors.lastname: Vargas
authors.forename: M F
authors.initials: MF
authors.lastname: Habashy
authors.forename: O
authors.initials: O
authors.lastname: Vesterqvist
authors.forename: C L
authors.initials: CL
authors.lastname: Delaney
authors.forename: W C
authors.initials: WC
authors.lastname: Liao
mesh_terms: D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000652:urine; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000652:urine*; D018660:Blood Pressure Monitoring, Ambulatory; D003404:Creatinine / Q000652:urine; D006152:Cyclic GMP / Q000652:urine; D004311:Double-Blind Method; D004573:Electrolytes / Q000652:urine; D005260:Female; D020022:Genetic Predisposition to Disease; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology*; D017706:Lisinopril / Q000494:pharmacology*; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D008875:Middle Aged; D011725:Pyridines / Q000494:pharmacology*; D012982:Sodium, Dietary / Q000008:administration & dosage*; D013841:Thiazepines / Q000494:pharmacology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004573:Electrolytes; D011725:Pyridines; D012982:Sodium, Dietary; D013841:Thiazepines; C106266:omapatrilat; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D003404:Creatinine; D017706:Lisinopril; D008666:Metalloendopeptidases; D006152:Cyclic GMP