Pharmacologic management of angioedema induced by angiotensin-converting enzyme inhibitors.
OBJECTIVE
The published evidence on pharmacologic approaches to the management of angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema is reviewed.


CONCLUSIONS
Angioedema is a serious, potentially life-threatening adverse effect of ACEI use. Although the underlying mechanism is not fully understood, excess bradykinin produced through a complex interplay between the kallikrein-kinin and renin-angiotensin-aldosterone systems is thought to play a major role. The nonallergic nature of the reaction renders traditional therapies (corticosteroids and antihistamines) ineffective because those agents do not modify the proposed pathophysiology. Fresh frozen plasma (FFP) provides kinase II, a protein that breaks down bradykinin. Case reports support FFP as a treatment for ACEI-induced angioedema, but no formal evaluations have been completed to date. Both ecallantide and complement 1 esterase (C1) inhibitor concentrate reduce bradykinin production through upstream inhibition of kallikrein. C1 inhibitor concentrate has been used successfully to manage ACEI-induced angioedema in a few reported cases, but robust supportive studies are lacking. Conversely, ecallantide has been evaluated in multiple randomized trials but has not been shown to offer advantages over traditional therapies. The use of icatibant, a direct antagonist of bradykinin B2 receptors, was reported to be beneficial in several case reports and in a small Phase II study, safely and rapidly reducing symptoms of ACEI-induced angioedema. An ongoing Phase III trial (NCT01919801) will better define the role of icatibant in the management of ACEI-induced angioedema.


CONCLUSIONS
FFP, C1 inhibitor, and icatibant appear to be safe and effective therapeutic options for the management of ACEI-induced angioedema, whereas it appears ecallantide should be avoided.
Department of Pharmacy Practice, Auburn University Harrison School of Pharmacy, Mobile, AL. mjs0065@auburn.edu.
Michael J
MJ
Scalese
Albert Einstein Medical Center, Philadelphia, PA.
Travis S
TS
Reinaker
D000799:Angioedema / Q000139:chemically induced* / Q000175:diagnosis / Q000188:drug therapy*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000627:therapeutic use; D050718:Complement C1 Inhibitor Protein / Q000627:therapeutic use; D019468:Disease Management; D006801:Humans; D010949:Plasma
D000806:Angiotensin-Converting Enzyme Inhibitors; D050718:Complement C1 Inhibitor Protein; C065679:icatibant; D001920:Bradykinin