What is the treatment for angioedema caused by Angiotensin-Converting Enzyme (ACE) inhibitors?

From the Guidelines

The primary treatment for angioedema caused by Angiotensin-Converting Enzyme (ACE) inhibitors is immediate discontinuation of the ACE inhibitor medication. This recommendation is based on the strongest and most recent evidence available, specifically from the study published in the Journal of Allergy and Clinical Immunology in 2013 1. The management of ACE-I–associated angioedema is discontinuation of the ACE-I, which is the cornerstone of therapy for these patients.

Key Considerations

• Discontinuation of the ACE inhibitor is crucial, although there might be a significant time lag between discontinuation of the drug and the propensity for angioedema.
• During acute attacks, patients need to be observed in a controlled environment in case they require intubation.
• Treatment with antihistamines, corticosteroids, or epinephrine has not been shown to be efficacious for ACE-I–associated angioedema, as noted in the study 1.
• Efficacy of icatibant and fresh frozen plasma have been described for ACE-I–associated angioedema; however, no controlled studies have been reported, as mentioned in the study 1.

Patient Education and Alternative Treatments

• Patients should be educated about this reaction and advised to seek immediate medical attention if they experience any facial, lip, tongue, or throat swelling while taking these medications.
• Once a patient has experienced ACE inhibitor-induced angioedema, they should never restart any ACE inhibitor as recurrence is likely.
• Alternative antihypertensive medications such as angiotensin receptor blockers (ARBs) can be considered, though with caution as there is a small risk (about 10%) of cross-reactivity.
• The mechanism behind ACE inhibitor-induced angioedema involves the accumulation of bradykinin due to inhibition of its breakdown by ACE, leading to increased vascular permeability and subsequent swelling, as explained in the study 1.

From the Research

Treatment Overview

• The primary focus for the treatment of angioedema caused by Angiotensin-Converting Enzyme (ACE) inhibitors is airway management 2.
• In the absence of high-quality evidence, no specific medication therapy is recommended for its treatment 2.
• If the treating physician feels the patient's presentation is more typical of an acute allergic reaction or anaphylaxis, it may be appropriate to treat for those conditions 2.

Medication Therapy

• Emerging evidence suggests that fresh frozen plasma (FFP), C1 esterase concentrate (C1-INH), ecallantide, and icatibant may be effective for use in ACE inhibitor-induced angioedema (ACEI-IA) 3.
• Off-label icatibant has the most evidence supporting its use in ACEI-IA with rapid symptom resolution and avoidance of intubation and tracheotomy in several cases 3.
• One study examining off-label use of icatibant has demonstrated efficacy over control, with rapid symptom improvement compared to corticosteroids and antihistamines 4.

Standard Pharmacotherapy

• Standard pharmacotherapy for ACEI-induced angioedema typically includes corticosteroids and antihistamines, although their efficacy has not been consistently demonstrated 4, 5.
• The use of corticosteroids and antihistamines has not been shown to cause harm, but their effectiveness in treating ACEI-induced angioedema is still a matter of debate 4, 6.

Discontinuation of ACE Inhibitors

• Any patient with suspected ACEI-induced angioedema should immediately discontinue the medication 2.
• Patients with a history of ACEI-induced angioedema should not be re-challenged with this class of agents, as there is a relatively high risk of recurrence 5.