title: Sustained antihypertensive actions of a dual angiotensin-converting enzyme neutral endopeptidase inhibitor, sampatrilat, in black hypertensive subjects.
abstract: Our objective was to evaluate the safety and antihypertensive efficacy of sampatrilat, a novel dual inhibitor of both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), in subjects poorly responsive to ACE inhibitor monotherapy. The ability of sampatrilat (50 to 100 mg daily) (n = 28) to lower blood pressure was compared with that of the ACE inhibitor lisinopril (10 to 20 mg daily) (n = 30) using a double-blind, randomized, parallel group study design over a 56-day treatment period in black hypertensives. Changes in systolic (SBP) and diastolic (DBP) blood pressure were determined using repeated ambulatory blood pressure (ABP) monitoring. Both sampatrilat and lisinopril decreased plasma ACE concentrations after 28 and 56 days. The decrease in plasma ACE concentrations (U/L) was greater after lisinopril (-9.33 +/- 0.52) as compared with sampatrilat (-6.31 +/- 0.70) (P = .0001) therapy. Lisinopril, but not sampatrilat, increased plasma renin activity. Lisinopril produced a transient decrease in mean 24-h ABP (mm Hg) at 28 days (SBP = -9.0 +/- 2.3, DBP = -5.7 +/- 1.3; P < .01), which returned to pretreatment values by 56 days of therapy. Alternatively, sampatrilat produced a sustained decrease in mean ABP over the 56-day treatment period (day 28: SBP = -7.3 +/- 1.8, DBP = -5.2 +/- 1.2; P < .01: day 56: SBP = -7.8 +/- 1.5; DBP = -5.2 +/- 0.95; P < 0.01) with a greater treatment effect on DBP than that of lisinopril at day 56 (P = .05). Treatment-emergent adverse events were noted to be similar between both treatment groups. We conclude that the antihypertensive actions of ACE/NEP inhibitor monotherapy in black subjects offers a novel therapeutic approach to patients otherwise resistant to the sustained antihypertensive actions of ACE inhibitor monotherapy.
authors.affiliation: Department of Physiology, University of Witwatersrand, Johannesburg, South Africa. 057nort@chiron.wits.ac.za
authors.forename: G R
authors.initials: GR
authors.lastname: Norton
authors.forename: A J
authors.initials: AJ
authors.lastname: Woodiwiss
authors.forename: C
authors.initials: C
authors.lastname: Hartford
authors.forename: B
authors.initials: B
authors.lastname: Trifunovic
authors.forename: S
authors.initials: S
authors.lastname: Middlemost
authors.forename: A
authors.initials: A
authors.lastname: Lee
authors.forename: M J
authors.initials: MJ
authors.lastname: Allen
mesh_terms: D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D044383:Black People; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006728:Hormones / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D017706:Lisinopril / Q000627:therapeutic use; D008297:Male; D008698:Mesylates / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D014443:Tyrosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D006728:Hormones; D008698:Mesylates; D014443:Tyrosine; D017706:Lisinopril; D015260:Neprilysin; C111998:sampatrilat