Treatment Options for Managing ACEI-Induced Angioedema

C1 inhibitor concentrate decreases production of bradykinin through upstream inhibition of kallikrein
C1 inhibitor concentrate decreases production of bradykinin through upstream inhibition of kallikrein

For the management of angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema, use of fresh frozen plasma and complement 1 esterase (C1) inhibitor appear to be safe and effective whereas ecallantide should be avoided, a study published in the American Journal of Health-System Pharmacy concluded. 

Angioedema is a serious and potentially life-threatening adverse effect of using ACEI. The excess production of bradykinin through the interaction of kallikrein-kinin and renin-angiotensin-aldosterone systems is thought to explain the mechanism, though it is not fully understood. Michael J. Scalese, PharmD, BCPS, and Travis S. Reinaker, PharmD, BCPS, reviewed the existing evidence on pharmacologic approaches to the management of ACEI-induced angioedema. 

Traditional agents such as corticosteroids and antihistamines are not effective because the reaction is non-allergic by nature and they do not alter the pathophysiology. Some case reports support the use of fresh frozen plasma to treat ACEI-induced angioedema as it provides a protein that breaks down bradykinin, kinase II. However, no formal studies have been conducted. 

Ecallantide and C1 inhibitor concentrate both decrease the production of bradykinin through upstream inhibition of kallikrein. A few cases have reported success with C1 inhibitor concentrate in managing ACE-induced angioedema "but robust supportive studies are lacking." Ecallantide, however, has been studied in multiple randomized trials but has not proven advantageous over traditional treatments. 

Icatibant, a direct antagonist of bradykinin B2 receptors, demonstrated a benefit in some case reports and a small Phase 2 study by quickly reducing the symptoms of ACE-induced angioedema. A Phase 3 trial currently underway will more clearly establish the role of icatibant in the management of ACE-induced angioedema. 

For more information visit ajhp.org.

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