Design of the omapatrilat in persons with enhanced risk of atherosclerotic events (OPERA) trial

Abstract

The Omapatrilat in Persons with Enhanced Risk of Atherosclerotic events (OPERA) trial is a large clinical trial of omapatrilat, a vasopeptidase inhibitor, in patients with stage 1 isolated systolic hypertension (ISH). OPERA is the first study to examine whether effective antihypertensive treatment can provide survival and clinical end point benefits in older persons with this common condition. This 5-year multinational, randomized, double-blind, parallel-group, placebo-controlled, forced-titration study will be conducted in approximately 12,600 subjects randomized by approximately 1100 study centers worldwide over a recruitment period of approximately 2 years. The primary objective of OPERA is to determine whether treatment with once-daily omapatrilat (target dose 40 mg) will reduce cardiovascular (CV) morbidity and mortality in older (> or = 65 years) men and women with enhanced risk for atherosclerotic events due to stage 1 ISH plus other risk factors for which currently there is no evidence-based requirement for treatment. Blood pressure inclusion criteria are systolic blood pressure (SBP) 140 to 159 mm Hg (SBP 125 to 139 mm Hg in diabetic individuals) and diastolic blood pressure (DBP) <90 mm Hg. The primary end point is defined as the composite of fatal/nonfatal stroke, fatal/nonfatal myocardial infarction, fatal/nonfatal heart failure, and other CV mortality. Secondary end points include the individual components of the primary end point, CV mortality, and major cardiovascular end points, as well as effects on cognitive function and initiation of treatment for diabetes. Additional analyses will be conducted in men and women, in diabetic patients, in different risk classes and according to prior evidence of vascular disease.

Pharmacological, Immunological, and Gene Targeting of the Renin-Angiotensin System for Treatment of Cardiovascular Disease

“…Although omapatrilat reduced systolic blood pressure more than enalapril in the Omapatrilat Cardiovascular Treatment Assessment Versus Enalapril (OCTAVE) clinical trial [135], the incidence of angioedema was more frequent with omapatrilat than enalapril (2.17% versus 0.68%). It would be interesting to see the results of the OC-TAVE mega study in Germany [136] and also of the Omapatrilat in Persons with Enhanced Risk of Atherosclerotic events (OPERA) trial that is designed to determine whether treatment with omapatrilat can reduce cardiovascular morbidity and mortality in older (>or=65 years) men and women with enhanced risk for atherosclerotic events [137].…”

Dual ACE/NEP inhibitors – more than playing the ACE card

“…26 However, more recently, the results of the omapatrilat versus enalapril randomized Trial of utility in reducing Events (OVERTURE) trial did not show a difference in the magnitude of improvement in ventricular size or function after 1 year when comparing omapatrilat to enalapril treatment in 321 patients with heart failure (NHHA classification II or more). 27,28 The Omapatrilat in Persons with Enhanced Risk of Atherosclerotic Events (OPERA) was planned to specifically investigate patients with high cardiovascular risk aged above 65 years and with hypertension, 29 however, was abandoned due to insufficient recruiting.…”

Vasopeptidase inhibitors: will they have a role in clinical practice?

“…With a decrease in cardiovascular death in the OVER-TURE study and previous studies showing potential benefit in patients with cardiovascular disease [85,86] perhaps the future of these agents will be in patients with clinical atherosclerotic diseases. The OPERA trial (omapatrilat in persons with enhanced risk of atherosclerotic events) addresses in part this issue by randomising high cardiovascular risk, older (> 65 years) hypertensive patients to see whether omapatrilat will reduce cardiovascular morbidity and mortality [87]. Other potential areas where vasopeptidase inhibitors may play a role (i.e.…”