What is the risk of angioedema when using an ARNI in combination with ACE inhibitors?
Available evidence demonstrates a potential signal of harm for a concomitant use of ACE inhibitors and ARNI. Oral neprilysin inhibitors, used in combination with ACE inhibitors can lead to angioedema and concomitant use is contraindicated and should be avoided. A medication that represented both a neprilysin inhibitor and an ACE inhibitor, omapatrilat, was studied in both hypertension and HF and was associated with a higher frequency of angioedema than that seen with enalapril in an RCT of patients with HFrEF.148 In a very large RCT of hypertensive patients, omapatrilat was associated with a 3-fold increased risk of angioedema as compared with enalapril.149 Blacks and smokers were particularly at risk.