A meta-analysis of 3 trials in HFrEF that compared combined neprilysin with RAAS inhibition with RAAS inhibition alone (IMPRESS [comparison of vasopeptidase inhibitor, omapatrilat, and lisinopril on exercise tolerance and morbidity in patients with heart failure]: omapatrilat vs lisinopril; OVERTURE: omapatrilat vs enalapril; and PARADIGM-HF: sacubitril-valsartan vs enalapril) demonstrated that combined neprilysin/RAAS inhibition was associated with a reduced incidence of a rise in serum creatinine and a less pronounced decline of GFR despite more hypotension.114. This evidence concerns the gene MME and heart failure.