Angioedema Triggered by Medication Blocking the Renin/Angiotensin System: Retrospective Study Using the French National Pharmacovigilance Database

J Clin Immunol. 2016 Jan;36(1):95-102. doi: 10.1007/s10875-015-0228-3. Epub 2015 Dec 28.

Abstract

Introduction: Bradykinin-mediated angioedema (AE) is a rare side effect of some medications, including angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB). In France, side-effects to treatments are reported to the national pharmacovigilance database.

Methods: The national MedDRA database was searched using the term "angioedema". Patients were included if they met the clinical criteria corresponding to bradykinin-mediated AE, if their C1-inhibitor levels were normal, and if they were treated with an ACEi or an ARB.

Results: 7998 cases of AE were reported between 1994 and 2013. Among these, 112 met the criteria for bradykinin-mediated AE with normal C1-inhibitor levels. On the 112 drug-AE, patients were treated with an ARB in 21% of cases (24 patients), or an ACEi in 77% of cases (88 patients), in combination with another treatment in 17 cases (mTORi for 3 patients, iDPP-4 for 1 patient, hormonal treatment for 7 patients). ENT involvement was reported in 90% of cases (tongue: 48.2%, larynx: 23.2%). The median duration of treatment before the first attack was 720 days, and the mean duration of attacks was 36.6 h. Forty-one percent (19/46) of patients relapsed after discontinuing treatment.

Conclusion: Angioedema triggered by medication blocking the renin/angiotensin system is rare but potentially severe, with a high risk of recurrence despite cessation of the causative drug.

Keywords: Angioedema; angiotensin II antagonist; angiotensin converting enzyme inhibitor; bradykinin.

MeSH terms

  • Aged
  • Angioedema / chemically induced
  • Angioedema / epidemiology*
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Bradykinin / administration & dosage*
  • Bradykinin / adverse effects
  • Databases, Factual
  • Female
  • France
  • Humans
  • Male
  • Pharmacovigilance
  • Recurrence
  • Renin-Angiotensin System / drug effects
  • Retrospective Studies
  • Withholding Treatment

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Bradykinin