Angioedema due to angiotensin-converting enzyme inhibitors

Angelo Agostoni, Marco Cicardi, Massimo Cugno, Lorenza C. Zingale, Daniela Gioffré, Jürg Nussberger

Research output: Contribution to journalArticlepeer-review


Angiotensin-converting enzyme (ACE) inhibitor associated angioedema was detected in 39 subjects (17%) of 231 consecutive patients examined in the last 5 years at our out-patient clinic for symptoms of angioedema without urticaria. In these patients, angioedema was most commonly localized to the face. The duration of ACE-inhibitor treatment at the onset of angioedema ranged from 1 day to 8 years with a median of 6 months. The time elapsed between onset of angioedema and withdrawal of ACE-inhibitor ranged from 1 day to 10 years with a median of 10 months. Delayed diagnosis is explained by the unusual characteristics of this adverse reaction: angioedema may start years after beginning the treatment and then it recurs irregularly. Infact, ACE-inhibitors seem to facilitate angioedema in predisposed subjects, rather than causing it with an allergic or idiosyncratic mechanism. Thus, while C1-inhibitor levels are usually normal in subjects developing ACE-inhibitor-dependent angioedema, we found that ACE-inhibitors caused angioedema in C1-inhibitor-deficient patients. Because the main inactivator of bradykinin is kininase II, which is identical with ACE, it is believed that bradykinin mediates ACE-inhibitor-dependent angioedema. We had the possibility to examine the plasma bradykinin levels in one ACE-inhibitor-treated patient during an angioedema attack and we found very high levels, but we did not find an increase of break-down products of high-molecular-weight-kininogen as observed during acute attacks in hereditary angioedema. Bradykinin fell to normal levels during remission after withdrawal of the drug. These observations indicate that in ACE-inhibitor-induced angioedema, contrary to hereditary angioedema, the reduction of bradykinin catabolic rate plays a predominant role. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)21-25
Number of pages5
Issue number1-2
Publication statusPublished - Oct 15 1999


  • Angioedema
  • Angiotensin-converting enzyme inhibitors
  • Bradykinin
  • C1-inhibitor
  • High-molecular-weight kininogen

ASJC Scopus subject areas

  • Pharmacology


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