With recognition that neprilysin inhibition by itself is ineffective and that the combination of neprilysin and ACE inhibition is associated with an increased risk of angioedema, the combination of angiotensin receptor and neprilysin inhibition was proposed as a safer and more effective option because ARBs do not increase bradykinin levels and are not associated with as much angioedema risk as ACE inhibitors. This evidence concerns the gene KNG1 and angioedema.