2000/06/01 by B Levine, Barton S. Levine
Medicine · #Coagulation, Bradykinin, Polyphosphates, and Angioedema #Heart Failure Treatment and Management #Renin-Angiotensin System Studies
paper · pdf · doi:10.1016/s0895-7061(00)01058-x
openalex publication_date 2000/06/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30
Omapatrilat (Oma), a novel vasopeptidase inhibitor, is a single molecule which inhibits both neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE). Inhibition of NEP protects endogenous vasodilators including the natriuretic peptides, bradykinin and adrenomedullin from degradation. In animal models of chronic renal disease, vasopeptidase inhibitors have compared favorably with ACE inhibitors. The goal of this 16 week, open-label study was to evaluate the safety, tolerability and antihypertensive efficacy of Oma monotherapy in subjects with impaired renal function. 89 subjects with a creatinine clearance (CrCl) ≤60 mL/min and trough seated diastolic BP (SeDBP) of 90–110 mmHg after withdrawal of all antihypertensives began treatment with Oma (10 mg titrated to 20 mg, 40 mg, or 80 mg as needed to reach a treatment target of trough SeDBP < 85 mmHg). 47% of patients received the 80 mg dose at week 16. Mean baseline BP was 161.9/100.7 mmHg and CrCl 36.5 mL/min. At the end of 16 weeks of Oma monotherapy, large and clinically important reductions in BP were observed: (See Table) Mean 24 hour urine protein excretion was reduced by 20% in subjects with baseline urine protein excretion ≥1 gram/24 hours. Mean serum creatinine increased modestly, similar to results observed with ACE inhibitors in renal disease patients. Increases in serum potassium were infrequent, mild, and transient, and never resulted in discontinuation from the study. In sum, Oma in subjects with renal disease produced reductions in BP exceeding those observed with ACE inhibitors or other monotherapies, reduced urine protein, and was safe and well-tolerated.