ACE inhibitor-mediated angioedema

Int Immunopharmacol. 2020 Jan:78:106081. doi: 10.1016/j.intimp.2019.106081. Epub 2019 Dec 10.


Angioedema (AE) occurring during ACE inhibitor therapy (ACEi-AE) is a rare complication involving between 0.1 and 0.7% of treated patients. AE can also complicate other therapeutic regimens that block the renin-angiotensin aldosterone system. Other drugs, such as immune suppressors, some type of antidiabetics or calcium antagonists, can increase the likelihood of ACEi-AE when associated to ACEi. There is a clear ethnic predisposition, since African-Americans or Hispanics show a higher prevalence of this condition compared to Caucasians. At least in African-Americans the genetic predisposition accounts for a general higher prevalence of AE, independently from the cause. People that experience ACEi-AE may have some recurrence when they are switched to an angiotensin-receptor blocker (ARB); however, epidemiological studies on large cohorts have shown that angiotensin receptor blockers (ARB) do not increase the likelihood of AE compared to other antihypertensives. Clinical manifestations consist of edema of face, lips, tongue, uvula and upper airways, requiring intubation or tracheotomy in severe cases. Attacks last for 48-72 h and require hospital admission in most cases. Intestinal involvement with sub-occlusive symptoms has also been reported. The pathogenesis of ACEi-AE depends mainly on a reduced catabolism and accumulation of bradykinin, which is normally metabolized by ACE. Genetic studies have shown that some single nucleotide polymorphisms at genes encoding relevant molecules for bradykinin metabolism and action may be involved in ACEi-AE, giving a basis for the ethnic predisposition. Treatment of ACEi-AE is still a matter of debate. Corticosteroids and antihistamines do not show efficacy. Some therapeutic attempts have shown some efficacy for fresh frozen plasma or C1 inhibitor concentrate infusion. Interventional studies with the specific bradykinin receptor antagonist icatibant have shown conflicting results; there might be a different ethnic predisposition to icatibant efficacy which has been proven in caucasian but not in black patients.

Publication types

  • Review

MeSH terms

  • Angioedema / chemically induced*
  • Angioedema / epidemiology
  • Angioedema / immunology
  • Angioedema / therapy
  • Angiotensin Receptor Antagonists / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects*
  • Black or African American
  • Blood Component Transfusion / methods
  • Bradykinin / analogs & derivatives
  • Bradykinin / immunology*
  • Bradykinin / metabolism
  • Bradykinin / therapeutic use
  • Bradykinin B2 Receptor Antagonists / therapeutic use
  • Complement C1 Inhibitor Protein / therapeutic use
  • Female
  • Humans
  • Hypertension / drug therapy*
  • Male
  • Peptidyl-Dipeptidase A / metabolism*
  • Plasma
  • Recurrence
  • Renin-Angiotensin System / drug effects
  • Risk Factors
  • Sex Factors


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Bradykinin B2 Receptor Antagonists
  • Complement C1 Inhibitor Protein
  • SERPING1 protein, human
  • icatibant
  • ACE protein, human
  • Peptidyl-Dipeptidase A
  • Bradykinin