2000/06/01 by P Larochelle, Pierre Larochelle
Medicine · #Blood Pressure and Hypertension Studies
paper · pdf · doi:10.1016/s0895-7061(00)00619-1
openalex publication_date 2000/06/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/29
This multicenter, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of the vasopeptidase inhibitor omapatrilat when given to subjects with isolated systolic hypertension (seated systolic blood pressure [SeSBP] 160–199 mm Hg and seated diastolic blood pressure [SeDBP] <90 mm Hg). After a 4-week placebo lead-in period, 429 subjects (mean age 66.7 years, baseline BP and pulse pressure [PP] 169.1/81.8 and 87.3 mm Hg, respectively) were randomized to receive 1 of 3 ompatrilat regimens (10 mg, 20 mg, or 20 mg increased to 40 mg at week 1) or matching placebo. The primary outcome measure was the change from baseline in trough SeSBP at week 9. Data (mean [SE]) are presented as change from baseline. At week 9, mean reductions in SeSBP in the omapatrilat 20 mg and 40 mg treatment regimens were clinically and statistically significant, as were changes in SeDBP and SePP: (See Table) P < 0.001 vs. placebo; P = 0.024 vs. placebo. P < 0.001 vs. placebo; P = 0.024 vs. placebo. In addition, omapatrilat administration did not adversely affect orthostatic BP or heart rate. At week 9, for omapatrilat-treated subjects the orthostatic changes were −1 to 1 mm Hg for SBP, −1 to 1 mm Hg for DBP, and −1 to 2 beats/minute for heart rate. At week 7, peak measurements of urinary atrial natriuretic peptide (ANP) excretion showed mean (baseline-adjusted), dose-related increases for omapatrilat regimens (+25.4, +32.4, and +50.5 pg/mg creatinine, respectively); placebo administration was without effect. Trough urinary ANP measurements showed sustained mean (baseline-adjusted) increases for omapatrilat 20 mg and 40 mg regimens (+5.7 and +11.1 pg/mg creatinine). The overall adverse event rates were higher than placebo but similar for all 3 omapatrilat regimens. Omapatrilat was effective and well tolerated when administered to subjects with isolated systolic hypertension.