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

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.