UMEM Educational Pearls

Title: C1-Esterase Inhibitor for ACE-Inhibitor Induced Angioedema

Category: Pharmacology & Therapeutics

Keywords: Angioedema, ACE-inhibitor, C1-Esterase Inhibitor, ACEi, C1INH, Berinert (PubMed Search)

Posted: 2/3/2023 by Wesley Oliver (Updated: 2/4/2023)
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ACE-inhibitor (ACEi) induced angioedema is mediated by bradykinin and there are no proven medications for the treatment of this disease. Theoretically, a C1-esterase inhibitor (C1INH) could be beneficial; however, data has not demonstrated any efficacy for these agents.  

Strassen et al. recently published a double-blind, randomized, controlled, multicenter trial of 30 patients comparing C1NH (Brand Name: Berinert) to placebo. In addition to standard treatment, a dose of C1INH (Berinert) 20 IU/kg or placebo (0.95% NaCl) was administered intravenously.

The primary endpoint was the time to complete resolution of signs and symptoms of edema (TCER). When compared to placebo, the original primary analysis demonstrated that the placebo arm (15 hours) resolved faster than the C1INH arm (24 hours, p=0.046).

This study is further evidence against the use of C1INH for ACE-inhibitor induced angioedema. The primary focus in the treatment of ACEi induced angioedema should continue to be airway management.

For reference, at our institution we have both C1INH (Berinert) and icatibant on formulary and they are restricted to only being used for acute hereditary angioedema attacks and cannot be used for ACEi induced angioedema.

References

Strassen U, et al. Efficacy of human C1 esterase inhibitor concentrate for treatment of ACE-inhibitor induced angioedema. Am J Emerg Med. 2023;64:121-128.

Wilkerson RG, Martinelli AN, Oliver WD. Treatment of angioedema induced by angiotensin-converting enzyme inhibitor [letter]. J Emerg Med. 2018;55:132-133.