Tolerance of bradykinin-releasing drugs in patients with acquired C1 inhibitor deficiency: a case series and review of the literature

Abstract

Background

As acquired angioedema (AAE) usually occurs in elder patients, the use of angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB) and dipeptidyl peptidase 4 inhibitors (DPP-4i) may be needed for cardiovascular or metabolic comorbidities. However, data are lacking regarding the tolerance of these bradykinin-releasing drugs in AAE patients.

Objectives

To report our experience of AAE patients exposed to bradykinin-releasing drugs and to review the available literature related to the tolerance of these agents in this disease.

Materials & Methods

Eligible patients were identified through screening of the patient database of the Lille National Reference Centre for bradykinin-mediated angioedema. Additional cases were detected by searching the available literature in the PubMed database. Patients were included if they were diagnosed with acquired C1-INH deficiency and exposed to at least one bradykinin-releasing drug (ACEi, ARB or DDP-4i).

Results

Overall, nine patients were included (three new cases and six previously reported cases). Most patients were diagnosed with AAE before or during drug exposure for variable periods of time. Drug exposure revealed the disease in six cases. ACEi were used in seven patients and appeared to be consistently poorly tolerated, with one case of fatal laryngeal attack. ARBs were used in three patients with no obvious effect on AAE attacks.

Conclusion

Angioedema attacks in patients exposed to bradykinin-releasing drugs should prompt an assessment of complement levels, as they may unmask an underlying C1-INH deficiency. Until further prospective data are available, the use of ACEi should be prohibited in AAE patients.