angioedema associated with ACE inhibitors

Last edited 10/2021 and last reviewed 11/2021

• this side effect occurs in approximately 1 % of users - but is much more common in the Afrocarribean population (circa 4%) (1)
  
  
• mechanism underlying the angio-oedema is likely to be the increased availability of bradykinin; this effect may also aggravate the angio-oedema associated with HAE. Angio-oedema associated with angiotensin receptor blockers has been reported infrequently and hence their use in individuals with ACE inhibitor-related angio-oedema has been questioned but is not contra-indicated (2)
  
  
• this side effect most commonly affects the face and mucous membranes, lips, tongue and larynx
  
  
• in general, symptoms are mild and short-lived
  
  
• in general this side effect occur within hours, or, at most weeks, after starting ACE inhibitor therapy - it reverses within hours of stopping treatment with the ACE inhibitor
  • however note that episodes of angio-oedema may persist for a few months after withdrawal of the ACE inhibitor without undermining the validity of the drug-related diagnosis
  • individuals of Afro-Caribbean origin are at increased risk of ACE inhibitor-induced angio-oedema and as these drugs are less effective in such individuals, an alternative antihypertensive may be prudent
  • antihistamines, corticosteroids and adrenaline are often used to treat these individuals although the efficacy of such treatment remains undetermined. C1 inhibitor concentrate is not beneficial in patients with acute angio-oedema associated with ACE inhibitors, although there are anecdotal reports of the benefit of fresh frozen plasma (2)
  • individuals who do not improve even after several months of stopping the ACE inhibitor, probably have idiopathic angio-oedema and are coincidentally taking an ACE inhibitor (2)
    • there are no routine investigations to distinguish responders from nonresponders to ACE inhibitor withdrawal
    • if the ACE inhibitor is responsible but is not withdrawn, the attacks may become more frequent and severe. ACE inhibitors are contra-indicated in subjects with a history of chronic angio-oedema, and alternative drugs should be used
    • CKS states (3)
      • for people taking an angiotensin-converting enzyme (ACE) inhibitor:
        • stop treatment immediately, and consider starting an alternative drug treatment.
        • if possible, avoid angiotensin-II receptor antagonists as these can also trigger episodes of angio-oedema

Reference:

1. Williams B, Poulter NR, Brown MJ, Davis M, McInnes GT, Potter JF, et al. Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society, 2004-BHS IV. J Hum Hypertens 2004;18: 139-85
2. Powell RJ et al; British Society for Allergy and Clinical Immunology (BSACI). BSACI guidelines for the management of chronic urticaria and angio-oedema.Clin Exp Allergy. 2007 May;37(5):631-50.
3. NICE Clinical Knowledge Summaries (CKS). Angio-oedema and anaphylaxis (accessed 27th October 2021).