A065: Double-blind withdrawal of omapatrilat after long-term stable administration demonstrates persistence of antihypertensive efficacy

• Published in: American journal of hypertension 2000-04, Vol.13 (S2), p.135A-135A
• Main Authors: Guthrie, R.M., Graff, A., Mroczek, W.J., El Hafi, S.E., Reeves, R.A.
• Format: Article
• Language: English
• Subjects: headache; long-term clinical trial; Omapatrilat; vasopeptidase inhibitors; withdrawal study
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1016/S0895-7061(00)00598-7

The persistence of an antihypertensive medication's action is rarely tested rigorously. Omapatrilat, a vasopeptidase inhibitor, has been effective in lowering blood pressure (BP) in long term clinical trials. As part of a large, ongoing, long-term (3 years) open-label study of once-daily oral omapatrilat in mild-to-moderate hypertension, 83 subjects, having received omapatrilat for > 6 months with seated diastolic BP (SeDBP) maintained < 90 mmHg on a stable dose of ≥20 mg for at least 2 months, were randomized to receive either continued stable omapatrilat dose or matching placebo (double-blind). Any open-label adjunctive antihypertensive medications were kept constant. Subjects continued on omapatrilat showed no changes in BP over the 8-week study period. In those subjects whose medication was replaced with placebo, there were clinically important increases in both systolic (16.5 mmHg) and diastolic (9.6 mmHg) BP, both significant relative to those who continued omapatrilat (p < 0.001), and 5/41 subjects withdrawn to placebo (12%) were discontinued for important rises in SeDBP (>100 mm Hg, confirmed). In addition, withdrawal to placebo was associated with a 22% incidence of new or worsening headaches, compared to 2.4% with continuous omapatrilat treatment. The overall frequency of any adverse clinical event reported during the study was 54% and 31% for placebo and omapatrilat, respectively. Conclusions: Replacement of omapatrilat by placebo during long-term administration was followed by clinically important and statistically significant increases in BP, demonstrating long-term persistence of omapatrilat's antihypertensive efficacy. Continued omapatrilat presented a better tolerability profile than withdrawal to placebo.