A classic example is the ACE/NEP inhibitor omapatrilatthat showed potent antihypertensive effects with beneficial effectson cardiac function heart failure patients.3,4 However,the OCTAVE study (Omapatrilat Cardiovascular Treatment AssessmentVersus Enalapril) was associated with a 3-fold higher incidence ofangioedema than observed for the ACE inhibitor enalapril, which ledto failure to receive FDA approval.5−8. This evidence concerns the gene ACE and heart failure.