From the Guidelines
ACE inhibitor-induced angioedema is a potentially life-threatening adverse reaction that requires immediate discontinuation of the offending medication, and patients who develop angioedema while taking an ACE inhibitor should have the drug stopped permanently and never restarted. The management of ACE inhibitor-induced angioedema includes airway assessment and, if needed, epinephrine 0.3-0.5 mg IM, antihistamines like diphenhydramine 25-50 mg IV/PO, and corticosteroids such as methylprednisolone 125 mg IV or prednisone 40-60 mg PO, as suggested by 1. For severe cases with airway compromise, immediate intubation may be necessary.
After resolution, patients should avoid all ACE inhibitors and consider alternative medications like angiotensin receptor blockers (ARBs), though there is a small risk of cross-reactivity, as noted in 1. The mechanism involves bradykinin accumulation due to decreased degradation by ACE inhibition, leading to vasodilation and increased vascular permeability. Unlike allergic angioedema, this reaction is not IgE-mediated, which explains why it can occur after years of uneventful ACE inhibitor use and why antihistamines and steroids may have limited effectiveness.
Some key points to consider in the management of ACE inhibitor-induced angioedema include:
- Discontinuation of the ACE inhibitor is the cornerstone of therapy, as stated in 1
- A modest risk of recurrent angioedema exists in patients who experienced angioedema in response to ACE-I therapy and then are switched to ARB therapy, as reported in 1
- The decision to switch to an ARB or to aliskiren when suspending an ACE-I because of angioedema should be considered in the context of a careful assessment of potential harm compared with benefit, as discussed in 1.
Overall, the priority in managing ACE inhibitor-induced angioedema is to ensure the patient's safety and prevent further episodes, as emphasized in 1.
From the Research
Definition and Incidence of ACE Inhibitor Angioedema
- Angioedema is a complication that has been reported in up to 1.0% of individuals taking angiotensin-converting enzyme inhibitors (ACE-Is) 2.
- The incidence of angioedema among patients who receive ACE-Is ranges from 0.1 to 0.7% 3.
- Angioedema occurs more frequently in African Americans, smokers, women, older individuals, and those with a history of drug rash, seasonal allergies, and use of immunosuppressive therapy 3.
Pathophysiology and Risk Factors
- The underlying pathophysiology of ACE-I-induced angioedema is incompletely understood, but is considered to be due in large part to excess bradykinin 2.
- The pathophysiology of ACE-I-induced angioedema involves inhibition of bradykinin and substance P degradation by ACE (kininase II) leading to vasodilator and plasma extravasation 3.
- High levels of bradykinin of different origin are associated with ACEI-induced angioedema, which preferentially occurs in females and in African-American populations 4.
Treatment and Management
- The primary focus for the treatment of ACE-I-AE is airway management 2.
- In the absence of high-quality evidence, no specific medication therapy is recommended for the treatment of ACE-I-AE 2.
- Treatment modalities include antihistamines, steroids, and epinephrine, as well as endotracheal intubation in cases of airway compromise 3.
- Patients with a history of ACE-I-induced angioedema should not be re-challenged with this class of agents, as there is a relatively high risk of recurrence 3.
Alternative Therapies
- Angiotensin II receptor blockers (AT2s) may be an alternative therapy for patients with a history of ACE-I-induced angioedema, as they do not increase the incidence of angioedema in these patients 5.
- However, some patients (<10%) with ACEI-associated angioedema also develop angioedema episodes after AT2 intake, so AT2s may be reserved for patients with high therapeutic need for angiotensin inhibition 4.