Comparison of vasopeptidase inhibitor, omapatrilat, and lisinopril on exercise tolerance and morbidity in patients with heart failure: IMPRESS randomised trial

Background We aimed to assess in patients with congestive heart failure whe ther dual inhibition of neutral endopeptidase and angiotensin-converting en zyme (ACE) with the vasopeptidase inhibitor omapatrilat is better than ACE inhibition alone with lisinopril on functional capacity and clinical outcom e. Methods We did a prospective, randomised, double-blind, parallel trial of 5 73 patients with New York Heart Association (NYHA) class It-IV congestive h eart failure, left-ventricular ejection fraction of 40% or less, and receiv ing an ACE inhibitor. Patients were randomly assigned omapatrilat at a dail y target dose of 40 mg (n=289) or lisinopril at a daily target dose of 20 m g (n=284) for 24 weeks, The primary endpoint was improvement in maximum exe rcise treadmill test (ETT) at week 12. Secondary endpoints included death a nd comorbid events indicative of worsening heart failure. Findings Week 12 ETT increased similarly in the omapatrilat and lisinopril groups 124 vs 31 s, p=0.45). The two drugs were fairly well tolerated, but there were fewer cardiovascular-system serious adverse events in the omapat rilat group than in the lisinopril group (20 [7%] vs 34 [12%], p=0.04). The re was a suggestive trend in favour of omapatrilat on the combined endpoint of death or admission for worsening heart failure (p=0.052; hazard ratio 0 .53 [95% CI 0.27-1.02]) and a significant benefit of omapatrilat in the com posite of death, admission, or discontinuation of study treatment for worse ning heart failure (p=0.035; 0.52 [0.28-0.96]). Omapatrilat improved NYHA c lass more than lisinopril in patients who had NYHA class III and IV (p=0.03 5), but not if patients with NYHA class II were included. Interpretation Our findings suggest that omapatrilat could have some advant ages over lisinopril in the treatment of patients with congestive vasopepti dase inhibitors heart could failure. Thus use of constitute a potentially i mportant treatment for further improving the prognosis and well being of pa tients with this disorder.