Omapatrilat in elderly hypertensive patients: A placebo-controlled trial

Omapatrilat, a novel vasopeptidase inhibitor (VPI), was assessed in elderly subjects with mild-to-moderate hypertension. 348 subjects, age ≥ 65 years with seated diastolic blood pressure (SeDBP) 95–110 mm Hg (mean age 71 years, baseline mean BP 163/99 mm Hg) were randomized to omapatrilat (10 mg, 20 mg, or 20 mg force-titrated to 40 mg at week 1) or matching placebo for 13 weeks. Data are presented as mean changes (SE) from baseline. Omapatrilat produced dose-related, statistically significant decreases in seated systolic blood pressure (SeSBP), SeDBP, and seated pulse pressure (SePP) relative to placebo: (See Table 1) Trough BP measured at week 9 (mm Hg); P = 0.027 vs. placebo; P < 0.001 vs. placebo; P = 0.013 vs. placebo. Trough BP measured at week 9 (mm Hg); P = 0.027 vs. placebo; P < 0.001 vs. placebo; P = 0.013 vs. placebo. Placebo-corrected reductions in SeSBP on the omapatrilat doses (−5.2, −10.7, −13.0 mm Hg) were more clearly dose-dependent and larger than the corresponding placebo-corrected reductions in SeDBP (−2.9, −4.4, −4.8 mm Hg). Elevations in peak urinary atrial natriuretic peptide (UrANP) excretion were dose-related: (See Table 2) Peak UrANP (pg/mg creatinine) measured at week 7. Peak UrANP (pg/mg creatinine) measured at week 7. Omapatrilat was safe and well tolerated, with similar overall adverse event rates between the 3 omapatrilat regimens. In conclusion, omapatrilat provided dose-related blood pressure reductions and was well tolerated in elderly patients with hypertension. Given the increased prevalence of systolic hypertension in older individuals, the ability of omapatrilat to control SeSBP may provide additional benefit.