Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial.

BACKGROUND Recent reports suggest that existing antihypertensive agents may not have sufficient efficacy to control blood pressure (BP) in many patients. Omapatrilat, an agent under development, has been shown to have significantly greater antihypertensive efficacy than existing agents, but may also carry increased risk of angioedema. We compared the efficacy and safety of omapatrilat to a representative angiotensin-converting enzyme (ACE) inhibitor, enalapril. METHODS The Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial is a multicenter, randomized, double-blind, active-controlled, 24-week trial in 25,302 patients with untreated or uncontrolled hypertension conducted in 3298 office-based sites in 12 countries. Subjects were randomized to omapatrilat 10 mg or enalapril 5 mg as initial therapy for hypertension (group 1, n = 9292), replacement for existing antihypertensive therapy (group 2, n =11,224), or in addition to existing antihypertensive therapy (group 3, n = 4751). Study drug was force-titrated at week 2 and electively titrated at weeks 4 and 6 to a maximum of omapatrilat 80 mg or enalapril 40 mg once daily. At weeks 8 and 16, adjunctive antihypertensive medications were added electively to achieve target BP. RESULTS Omapatrilat reduced systolic BP 3.6 mm Hg more than enalapril at week 8, and was associated with less use of adjunctive antihypertensive therapy by week 24 (19% v 27%; P < 0.001 for both comparisons). Subjects randomized to omapatrilat were more likely to reach BP target, regardless of demographics or comorbid conditions and whether omapatrilat was used as initial therapy, replacement for existing therapy, or in addition to existing therapy. Angioedema was more frequent with omapatrilat than enalapril (2.17% v 0.68%). Two omapatrilat-treated subjects experienced angioedema with airway compromise, which was successfully treated. CONCLUSIONS Omapatrilat provided broadly superior antihypertensive efficacy when used in a setting resembling clinical practice. Angioedema was more common than with enalapril but life-threatening angioedema was rare. The risk-benefit profile for omapatrilat in clinical use therefore appears likely to be favorable in appropriate patients.