Abstract
No specific drugs are licensed for the treatment of ACE inhibitor (ACEI)-acquired angioedema (ACEI-AAE). Icatibant, an antagonist of the B2 receptor of bradykinin, is a potential treatment for this condition; however, its use in this setting is poorly documented. We report here clinical outcomes of 13 patients with ACEI-AAE treated with icatibant, in a real-life setting. Thirteen patients on ACEI seen in an Emergency Department (ED) with angioedema involving face, lips or the upper airways were analyzed. Angioedema due to known causes other than ACEI treatment was excluded. Initially, all patients received standard therapy (antihistamine, corticosteroids and epinephrine). Due to the lack of response and a worsening severity of symptoms, all patients received one subcutaneous injection of icatibant (30 mg/mL). Following icatibant treatment, all patients experienced improvement in the symptoms. The median time from onset of clinical symptoms to injection of icatibant was 3 h (IQR 2.5–5.5 h). Symptom relief was reported at 30 min (IQR 27.5–70 min). A complete resolution of symptoms was observed at 5 h (IQR 4–7 h). Ten patients had previously experienced angioedema attacks. The Median time to complete resolution of the previous attacks was higher (54 h; IQR 33–63 h), than after icatibant (p = 0.002) therapy. No patients required tracheal intubation or tracheotomy, and all patients were discharged within 24 h. No adverse events were reported. Before discharge, all patients were instructed to discontinue ACEI, and to take a different antihypertensive agent. This case series supports the efficacy of icatibant in improving symptoms of ACEI-AAE.
Similar content being viewed by others
References
Byrd JB, Adam A, Brown NJ (2006) Angiotensin-converting enzyme inhibitor-associated angioedema. Immunol Allergy Clin North Am 26:725–737
Bas M, Greve J, Stelter K, Bier H, Stark T et al (2010) Therapeutic efficacy of icatibant in angioedema induced by angiotensin-converting enzyme inhibitors: a case series. Ann Emerg Med 56:278–282
Hoover T, Lippmann M, Grouzmann E, Marceau F, Herscu P (2010) Angiotensin converting enzyme inhibitor induced angio-oedema: a review of the pathophysiology and risk factors. Clin Exp Allergy 40:50–61
Cicardi M Aberer W, Banerji A, Bas M, Bernstein JA, et al (2014) Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group. Allergy, (Epub ahead of print)
Cicardi M, Zingale LC, Bergamaschini L, Agostoni A (2004) Angioedema associated with angiotensin-converting enzyme inhibitor use: outcome after switching to a different treatment. Arch Intern Med 164:910–913
Miller DR, Oliveria SA, Berlowitz DR, Fincke BG, Stang P, Lillienfeld DE (2008) Angioedema incidence in US veterans initiating angiotensin-converting enzyme inhibitors. Hypertension 51:1624–1630
Makani H, Messerli FH, Romero J, Wever-Pinzon O, Korniyenko A et al (2012) Meta-analysis of randomized trials of angioedema as an adverse event of renin-angiotensin system inhibitors. Am J Cardiol 110:383–391
Banerji A, Clark S, Blanda M, LoVecchio F, Snyder B, Camargo CA Jr (2008) Multicenter study of patients with angiotensin-converting enzyme inhibitor-induced angioedema who present to the emergency department. Ann Allergy Asthma Immunol 100:327–332
Beltrami L, Zanichelli A, Zingale L, Vacchini R, Carugo S, Cicardi M (2011) Long-term follow-up of 111 patients with angiotensin-converting enzyme inhibitor-related angioedema. J Hypertens 29:2273–2277
Manders K, van Deuren M, Hoedemaekers C, Simon A (2012) Bradykinin-receptor antagonist icatibant: possible treatment for ACE inhibitor-related angio-oedema. Neth J Med 70:386–387
Nielsen EW, Gramstad S (2006) Angioedema from angiotensin-converting enzyme (ACE) inhibitor treated with complement 1 (C1) inhibitor concentrate. Acta Anaesthesiol Scand 50:120–122
Baram M, Kommuri A, Sellers SA, Cohn JR (2013) ACE inhibitor-induced angioedema. J Allergy Clin Immunol Pract 1:442–445
Bouillet L, Ponard D, Drouet C, Massot C (2004) Non-histaminic angiodema management: diagnostic and therapeutic interest of tranexamic acid. Rev Med Interne 25:924–926
Cugno M, Zanichelli A, Foieni F, Caccia S, Cicardi M (2009) C1-inhibitor deficiency and angioedema: molecular mechanisms and clinical progress. Trends Mol Med 15:69–78
Zanichelli A, Bova M, Coerezza A, Petraroli A, Triggiani M, Cicardi M (2012) Icatibant treatment for acquired C1-inhibitor deficiency: a real-world observational study. Allergy 67:1074–1077
Illing EJ, Kelly S, Hobson JC, Charters S (2012) Icatibant and ACE inhibitor angioedema. BMJ Case Rep. doi: 10.1136/bcr-2012-006646
Fast S, Henningsen E, Bygum A (2011) Icatibant is a new treatment option in life-threatening angioedema triggered by angiotensin-converting enzyme inhibitor. UgeskrLaeger 173:2574–2575
Gallitelli M, Alzetta M (2012) Icatibant: a novel approach to the treatment of angioedema related to the use of angiotensin-converting enzyme inhibitors. Am J Emerg Med 30:1664.e1–1664.e2
Javaud N, Fain O, Bernot B, Adnet F, Lapostolle F (2011) Bradykinin-mediated angioedema secondary to angiotensin converting enzyme: initiate treatment from the prehospital phase. Ann Fr Anesth Reanim 30:848–850
Volans A, Ferguson R (2013) Using a bradykinin blocker in ACE inhibitor-associated angioedema in the emergency department. BMJ Case Rep. doi: 10.1136/bcr-2012-008295
Zanichelli A, Badini M, Nataloni I, Montano N, Cicardi M (2011) Treatment of acquired angioedema with icatibant: a case report. Intern Emerg Med 6:279–280
Brown NJ, Byiers S, Carr D, Maldonado M, Warner BA (2009) Dipeptidyl peptidase-IV inhibitor use associated with increased risk of ACE inhibitor-associated angioedema. Hypertension 54:516–523
Cicardi M, Bellis P, Bertazzoni G, Cancian M, Chiesa M, Cremonesi P, Marino P, Montano N, Morselli C, Ottaviani F, Perricone R, Triggiani M, Zanichelli A (2014) Guidance for diagnosis and treatment of acute angioedema in the emergency department: consensus statement by a panel of Italian experts. Intern Emerg Med 9:85–92
Acknowledgments
Editorial assistance was provided by Luca Giacomelli, PhD with the support of the Associazione Italiana per lo Studio, la Diagnosi e la Terapia dell’Angioedema Ereditario.
Conflict of interests
Maria Bova has received sponsorship for educational purposes, has been paid for providing consultancy services, and has taken part in clinical trials sponsored by Shire, Pharming NV, CSL-Behring and SOBI. Mar Guilarte has received sponsorship for educational purposes and consultancy services, and has taken part in clinical trials sponsored by Shire, Pharming NV, CSL-Behring and Viropharma Inc. Anna Sala-Cunill has received sponsorship for educational purposes, has been paid for providing consultancy services, and has taken part in clinical trials sponsored by Shire, Pharming NV, CSL-Behring and Viropharma Inc. Grazia Maria Luisa Rizzelli has received sponsorship for educational purposes by Shire. Andrea Zanichelli has received speaker fees from CSL Behring, Shire, SOBI and ViroPharma, and consultancy fees from CSL Behring, Shire and ViroPharma. No funding (e.g. in terms of drug provision) was required for this case series.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bova, M., Guilarte, M., Sala-Cunill, A. et al. Treatment of ACEI-related angioedema with icatibant: a case series. Intern Emerg Med 10, 345–350 (2015). https://doi.org/10.1007/s11739-015-1205-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11739-015-1205-9