Randomized double-blind comparison of omapatrilat with amlodipine in mild-to-moderate hypertension

Abstract

The antihypertensive efficacy of the vasopeptidase inhibitor, omapatrilat, was compared with the calcium channel blocker, amlodipine, using ambulatory blood pressure monitoring (ABPM) in a 10-week double-blind trial. 430 subjects age ≥18 years (mean age 53.7 years) with diastolic blood pressure (DBP) 95–110 mmHg were randomized into 2 parallel groups. One group received once-daily omapatrilat 20 mg for 2 weeks, 40 mg for 2 weeks, then 80 mg for 6 weeks; and the second, amlodipine 5 mg for 2 weeks, then 10 mg for 8 weeks [forced titration]. After all prior antihypertensive medications had been discontinued, 24-hour ABPM was used to establish baseline values for ambulatory BP parameters: systolic BP (ASBP), diastolic BP (ADBP), and mean BP (AMBP). 24-hour ABPM was repeated after 10 weeks of double-blind treatment and change from baseline for ambulatory BP parameters was determined. At 10 weeks, omapatrilat 80 mg had produced clinically important and statistically significant greater reductions in all ambulatory BP parameters than did amlodipine 10 mg, including the last 2 hours of recording: (See Table) Mean (SE) in mm Hg; P < 0.001 vs. amlodipine. Mean (SE) in mm Hg; P < 0.001 vs. amlodipine. The ambulatory values over 24 hours showed that both agents had persistent pharmacologic activity, compatible with once-daily dosing. Omapatrilat was safe and well tolerated with overall adverse event and discontinuation rates lower than with amlodipine. In conclusion, omapatrilat 80 mg produced superior blood pressure lowering compared with amlodipine 10 mg (maximum recommended dose), as assessed by ABPM.