What is the management of Angiotensin-Converting Enzyme (ACE) inhibitor-induced angioedema?

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Last updated: April 7, 2025View editorial policy

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From the Guidelines

Discontinuation of the ACE inhibitor is the cornerstone of therapy for patients with ACE inhibitor-induced angioedema. The management of ACE inhibitor-induced angioedema requires immediate discontinuation of the offending medication, as stated in the 2013 update by the Journal of Allergy and Clinical Immunology 1. During acute attacks, patients need to be observed in a controlled environment in case they require intubation.

Key Considerations

  • Discontinuation of the ACE inhibitor may not immediately resolve the angioedema, as there can be a significant time lag between discontinuation of the drug and the propensity for angioedema 1.
  • Treatment with antihistamines, corticosteroids, or epinephrine has not been shown to be efficacious for ACE inhibitor-induced angioedema 1.
  • Efficacy of icatibant and fresh frozen plasma have been described for ACE inhibitor-associated angioedema, although no controlled studies have been reported 1.

Treatment Approach

  • For mild cases, observation may be sufficient, while for moderate to severe cases, securing the airway and administering specific treatments such as icatibant or C1 esterase inhibitor concentrate may be necessary.
  • After resolution, patients should permanently avoid all ACE inhibitors and be counseled that angiotensin receptor blockers (ARBs) are generally safe alternatives.

Pathophysiology

  • ACE inhibitor-induced angioedema occurs due to excessive bradykinin accumulation when ACE, which normally degrades bradykinin, is inhibited, leading to vasodilation and increased vascular permeability.

From the Research

Management of ACE Inhibitor-Induced Angioedema

  • The primary focus for the treatment of ACE inhibitor-induced angioedema 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.
  • Any patient with suspected ACE inhibitor-induced angioedema should immediately discontinue that medication 2, 3, 4.

Treatment Modalities

  • Antihistamines, steroids, and epinephrine may be used as treatment modalities 3, 5.
  • Endotracheal intubation may be necessary in cases of airway compromise 3.
  • Fresh frozen plasma (FFP) has been used successfully in the treatment of resistant, life-threatening angioedema due to an ACE inhibitor 6.
  • Bradykinin antagonists, kallikrein inhibitor, and C1 inhibitor may also be considered, although their efficacy has not been consistently demonstrated 5.

Prevention

  • Patients with a history of ACE inhibitor-induced angioedema should not be re-challenged with this class of agents, as there is a relatively high risk of recurrence 3.
  • ACE inhibitors should be avoided in high-risk individuals, such as African Americans, smokers, women, older individuals, and those with a history of drug rash, seasonal allergies, and use of immunosuppressive therapy 3, 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

ACE Inhibitor-Induced Angioedema: a Review.

Current hypertension reports, 2018

Research

Pharmacotherapy for Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema: A Systematic Review.

Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 2018

Research

Fresh frozen plasma in the treatment of resistant angiotensin-converting enzyme inhibitor angioedema.

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, 2004

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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