What is the mainstay of treatment for angioedema associated with Angiotensin-Converting Enzyme (ACE) inhibitors?

From the Guidelines

The mainstay of treatment for angioedema associated with angiotensin-converting enzyme (ACE) inhibitors is immediate discontinuation of the ACE inhibitor medication. This approach is based on the strongest and most recent evidence, which emphasizes the importance of stopping the offending medication to prevent further episodes of angioedema 1. The management of ACE-I (or ARB)–associated angioedema is discontinuation of the ACE-I (or ARB), as stated in the guidelines 1.

Key Considerations

• Discontinuation of the ACE inhibitor is the cornerstone of therapy for patients with ACE-I–associated angioedema, although there might be a significant time lag between discontinuation of the drug and the propensity for angioedema 1.
• 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 this type of angioedema, as it is bradykinin-mediated rather than histamine-mediated 1.
• Efficacy of icatibant and fresh frozen plasma have been described for ACE-I–associated angioedema; however, no controlled studies have been reported 1.

Supportive Care

Supportive care is then provided based on symptom severity, including airway management if there is respiratory compromise. For severe cases affecting the airway, intubation or even emergency tracheostomy may be necessary. After resolution, patients should never be rechallenged with ACE inhibitors and should instead be prescribed alternative antihypertensive medications, preferably avoiding angiotensin receptor blockers (ARBs) which, though rarely, can also cause similar reactions 1.

Mechanism and Risk Factors

The mechanism behind ACE inhibitor-associated angioedema involves the drug's inhibition of ACE, which normally degrades bradykinin, resulting in bradykinin accumulation that increases vascular permeability and causes the characteristic swelling. African American subjects are at a substantially higher risk of experiencing ACE-I–induced angioedema than white subjects, and other factors that increase the risk include a history of smoking, increasing age, and female sex 1.

From the Research

Treatment Options for Angioedema Associated with Angiotensin-Converting Enzyme Inhibitors

• The mainstay of treatment for angioedema associated with angiotensin-converting enzyme (ACE) inhibitors includes:
  • Supportive care, such as cessation of the inciting agent, steroids, antihistamines, and epinephrine, if not otherwise contraindicated 2
  • First-line therapies include ACEI discontinuation, observation, and supportive medications (eg, corticosteroids, antihistamines, and epinephrine) 3
• Other treatment options that have shown promise in managing ACEI-induced angioedema include:
  • Fresh frozen plasma (FFP) 3, 4
  • C1 esterase inhibitor (C1-INH) 3, 5
  • Icatibant, a bradykinin antagonist 3
• It is essential to note that no medications are currently Food and Drug Administration-approved for managing ACEI-induced angioedema, and treatment is often based on the severity of symptoms and the patient's response to initial therapies 3

Pathophysiology and Risk Factors

• The pathophysiology of ACEI-induced angioedema involves inhibition of bradykinin and substance P degradation by ACE (kininase II) leading to vasodilator and plasma extravasation 6
• Risk factors for ACEI-induced angioedema include African American ethnicity, smoking, female sex, older age, and a history of drug rash, seasonal allergies, and use of immunosuppressive therapy 6

Clinical Considerations

• 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 6
• Early diagnosis and treatment are crucial in preventing airway compromise and other complications associated with ACEI-induced angioedema 3, 6