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.
CONCLUSION: