ACE Inhibitor-Induced Angioedema: a Review

Current Hypertension Reports

Volumn 20, Issue 7, 2017, Pages

  Kostis, William J ^a   Shetty, Mrinali ^b   Chowdhury, Yuvraj Singh ^b   Kostis, John B ^a  

^a ROBERT WOOD JOHNSON MEDICAL SCHOOL   (United States)

^b SAINT PETER S UNIVERSITY HOSPITAL   (United States)

Author keywords

Angioedema; Angiotensin II; Angiotensin converting enzyme inhibitors; Bradykinin; Hypertension

Indexed keywords

ALISKIREN; ANGIOTENSIN RECEPTOR ANTAGONIST; BRADYKININ; DIPEPTIDYL CARBOXYPEPTIDASE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENKEPHALINASE INHIBITOR; SUBSTANCE P; ANTIHISTAMINIC AGENT; CORTICOSTEROID; EPINEPHRINE;

AFRICAN AMERICAN; ALLERGY; ANGIONEUROTIC EDEMA; DRUG ERUPTION; ENDOTRACHEAL INTUBATION; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; INCIDENCE; MEDICAL HISTORY; PATHOPHYSIOLOGY; REVIEW; SMOKING; CAPILLARY PERMEABILITY; DRUG EFFECT; FEMALE; HYPERTENSION; MULTIMODALITY CANCER THERAPY; RISK FACTOR; VASODILATATION;

ADRENAL CORTEX HORMONES; ANGIOEDEMA; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; BRADYKININ; CAPILLARY PERMEABILITY; COMBINED MODALITY THERAPY; EPINEPHRINE; FEMALE; HISTAMINE ANTAGONISTS; HUMANS; HYPERTENSION; INTUBATION, INTRATRACHEAL; RISK FACTORS; SUBSTANCE P; VASODILATION;

EID: 85048297681     PISSN: 15226417     EISSN: 15343111     Source Type: Journal    
DOI: 10.1007/s11906-018-0859-x     Document Type: Review

References (59)

1. Osler W. Hereditary angio-neurotic oedema. Am J Med Sci. 1888;95:362–7.
2. Hedner T, Samuelsson O, Lunde H, Lindholm L, Andrén L, Wiholm BE. Angio-oedema in relation to treatment with angiotensin converting enzyme inhibitors. BMJ. 1992;304:941–6.
3. Nussberger J, Cugno M, Cicardi M. Bradykinin-mediated angioedema. N Engl J Med. 2002;347:621–2.
4. Lin RY, Cannon AG, Teitel AD. Pattern of hospitalizations for angioedema in New York between 1990 and 2003. Ann Allergy Asthma Immunol. 2005;95:159–66.
5. IQVIA Institute for Human Data Science. Medicines use and spending in the U.S. [Internet]. 2017 May. Available from: https://www.iqvia.com/institute/reports/medicines-use-and-spending-in-the-us-a-review-of-2016.
6. Lin RY, Shah SN. Increasing hospitalizations due to angioedema in the United States. Am Coll Allergy Asthma Immunol. 2008;101:185–92.
7. Ferreira SH. A bradykinin-potentiating factor (BPF) present in the venom of Bothrops jararaca. Br J Pharmacol Chemother. 1965;24:163–9.
8. Bakhle YS. Conversion of angiotensin I to angiotensin II by cell-free extracts of dog lung. Nature. 1968;220:919–21.
9. Ondetti MA, Rubin B, Cushman DW. Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents. Science. 1977;196:441–4.
10. Cushman DW, Ondetti MA. History of the design of captopril and related inhibitors of angiotensin converting enzyme. Hypertension. 1991;17:589–92.
11. Yang HY, Erdös EG, Levin Y. A dipeptidyl carboxypeptidase that converts angiotensin I and inactivates bradykinin. Biochim Biophys Acta. 1970;214:374–6.
12. Nussberger J, Cugno M, Amstutz C, Cicardi M, Pellacani A, Agostoni A. Plasma bradykinin in angio-oedema. Lancet. 1998;351:1693–7.
13. • Byrd JB, Touzin K, Sile S, Gainer JV, Yu C, Nadeau J, et al. Dipeptidyl peptidase IV in angiotensin-converting enzyme inhibitor associated angioedema. Hypertension. 2008;51:141–7. This study demonstrated a decrease of dipeptidyl peptidase IV activity and antigen in sera of patients with ACE-I induced angioedema as compared to ACE-I exposed control subjects who did not develop angioedema.
14. Ni H, Li L, Liu G, Hu S-Q. Inhibition mechanism and model of an angiotensin I-converting enzyme (ACE)-inhibitory hexapeptide from yeast (Saccharomyces cerevisiae). Cox D, editor. PLoS One. 2012;7:e37077–7.
15. Kostis JB. Angiotensin converting enzyme inhibitors. I. Pharmacology. Am Heart J. 1988;116:1580–91.
16. Marceau F, Hess JF, Bachvarov DR. The B1 receptors for kinins. Pharmacol Rev. 1998;50:357–86.
17. Cugno M, Nussberger J, Cicardi M, Agostoni A. Bradykinin and the pathophysiology of angioedema. Int Immunopharmacol. 2003;3:311–7.
18. Israili ZH, Hall WD. Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy. A review of the literature and pathophysiology. Ann Intern Med. 1992;117:234–42.
19. Byrd JB, Shreevatsa A, Putlur P, Foretia D, McAlexander L, Sinha T, et al. Dipeptidyl peptidase IV deficiency increases susceptibility to angiotensin-converting enzyme inhibitor-induced peritracheal edema. J Allergy Clin Immunol. 2007;120:403–8.
20. Adam A, Cugno M, Molinaro G, Perez M, Lepage Y, Agostoni A. Aminopeptidase P in individuals with a history of angio-oedema on ACE inhibitors. Lancet. 2002;359:2088–9.
21. Abbud ZA, Wilson AC, Cosgrove NM, Kostis JB. Angiotensin-converting enzyme gene polymorphism in systemic hypertension. Am J Cardiol. 1998;81:244–6.
22. Gulec M, Caliskaner Z, Tunca Y, Ozturk S, Bozoglu E, Gul D, et al. The role of ace gene polymorphism in the development of angioedema secondary to angiotensin converting enzyme inhibitors and angiotensin II receptor blockers. Allergol Immunopathol (Madr). 2008;36:134–40.
23. Pare G, Kubo M, Byrd JB, McCarty CA, Woodard-Grice A, Teo KK, et al. Genetic variants associated with angiotensin-converting enzyme inhibitor-associated angioedema. Pharmacogenet Genomics. 2013;23:470–8.
24. • Woodard-Grice AV, Lucisano AC, Byrd JB, Stone ER, Simmons WH, Brown NJ. Sex-dependent and race-dependent association of XPNPEP2 C-2399A polymorphism with angiotensin-converting enzyme inhibitor-associated angioedema. Pharmacogenet Genomics. 2010;20:532–6. This case control study showed that polymorphism of XPNPEP2 C-2399A (a genotype associated with serum aminopeptidase P activity) was associated with ACE-I induced angioedema in men but not in women.
25. • Rasmussen E, Mey K, Bygum A. Angiotensin-converting enzyme inhibitor-induced angioedema—a dangerous new epidemic. Acta Derm Venerol. 2014;94:260–4. This review article from a dermatology perspective discusses ACE-I induced angioedema, its prognosis and treatment options.
26. Hoover T, Lippmann M, Grouzmann E, Marceau F, Herscu P. Angiotensin converting enzyme inhibitor induced angio-oedema: a review of the pathophysiology and risk factors. Clin Exp Allergy. 2009;40:733–12.
27. Kostis J. Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial. Am J Hypertens. 2004;17:103–11.
28. • Kostis JB, Kim HJ, Rusnak J, Casale T, Kaplan A, Corren J, et al. Incidence and characteristics of angioedema associated with enalapril. Arch Intern Med. 2005;165:1637–42. This is the only randomized controlled clinical trial with blind adjudication of angioedema by a committee of angioedema experts.
29. Slater EE, Merrill DD, Guess HA, Roylance PJ, Cooper WD, Inman WH, et al. Clinical profile of angioedema associated with angiotensin converting-enzyme inhibition. JAMA. 1988;260:967–70.
30. Messerli FH, Nussberger J. Vasopeptidase inhibition and angio-oedema. Lancet. 2000;356:608–9.
31. Miller DR, Oliveria SA, Berlowitz DR, Fincke BG, Stang P, Lillienfeld DE. Angioedema incidence in US veterans initiating angiotensin-converting enzyme inhibitors. Hypertension. 2008;51:1624–30.
32. Makani H, Messerli FH, Romero J, Wever-Pinzon O, Korniyenko A, Berrios RS, et al. Meta-analysis of randomized trials of angioedema as an adverse event of renin–angiotensin system inhibitors. Am J Cardiol. 2012;110:383–91.
33. Banerji A, Clark S, Blanda M, LoVecchio F, Snyder B, Camargo CA. Multicenter study of patients with angiotensin-converting enzyme inhibitor-induced angioedema who present to the emergency department. Ann Allergy Asthma Immunol. 2008;100:327–32.
34. • Vasekar M, Craig TJ. ACE inhibitor-induced angioedema. Curr Allergy Asthma Rep. 2011;12:72–8. A comprehensive review of ACE-I induced angioedema with emphasis on application of drugs used in hereditary angioedema in the management of ACE-I induced angioedema.
35. Lefebvre J, Murphey LJ, Hartert TV, Jiao Shan R, Simmons WH, Brown NJ. Dipeptidyl peptidase IV activity in patients with ACE-inhibitor-associated angioedema. Hypertension. 2002;39:460–4.
36. Kostis WJ, Cabrera J, Daeumer J, Chowdhury YS, Shetty M, Kostis JB. Prediction of angioedema among 12,557 patients receiving enalapril. Circulation. 2017;136:A13789.
37. Brown NJ, Ray WA, Snowden M, Griffin MR. Black Americans have an increased rate of angiotensin converting enzyme inhibitor-associated angioedema. Clin Pharmacol Ther. 1996;60:8–13.
38. Gainer JV, Nadeau JH, Ryder D, Brown NJ. Increased sensitivity to bradykinin among African Americans. J Allergy Clin Immunol. 1996;98:283–7.
39. Gibbs CR, Lip GY, Beevers DG. Angioedema due to ACE inhibitors: increased risk in patients of African origin. Br J Clin Pharmacol. 1999;48:861–5.
40. Dean DE, Schultz DL, Powers RH. Asphyxia due to angiotensin converting enzyme (ACE) inhibitor mediated angioedema of the tongue during the treatment of hypertensive heart disease. J Forensic Sci. 2001;46:1239–43.
41. Caballero T, Baeza ML, Cabañas R, Campos A, Cimbollek S, Gómez-Traseira C, et al. Consensus statement on the diagnosis, management, and treatment of angioedema mediated by bradykinin. Part II. Treatment, follow-up, and special situations. J Investig Allergol Clin Immunol. 2011;21:422–41.
42. Walford HH, Zuraw BL. Current update on cellular and molecular mechanisms of hereditary angioedema. Ann Allergy Asthma Immunol. 2014;112:413–8.
43. • Duerr M, Glander P, Diekmann F, Dragun D, Neumayer HH, Budde K. Increased incidence of angioedema with ACE inhibitors in combination with mTOR inhibitors in kidney transplant recipients. Clin J Am Soc Nephrol. 2010;5:703–8. This study demonstrates a significantly higher incidence (6.6%) of angioedema in kidney transplant patients receiving both mTOR inhibitors and ACE-I as compared to either drug alone.
44. Brown NJ, Snowden M, Griffin MR. Recurrent angiotensin-converting enzyme inhibitor-associated angioedema. JAMA. 1997;278(3):232–3.
45. Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ. 2003;326:1419–0.
46. Indian Polycap Study (TIPS). Effects of a polypill (Polycap) on risk factors in middle-aged individuals without cardiovascular disease (TIPS): a phase II, double-blind, randomised trial. Lancet. 2009;373:1341–51.
47. Craig TJ, Bernstein JA, Farkas H, Bouillet L, Boccon-Gibod I. Diagnosis and treatment of bradykinin-mediated angioedema: outcomes from an angioedema expert consensus meeting. Int Arch Allergy Immunol. 2014;165:119–27.
48. • Baş M, Greve J, Stelter K, Havel M, Strassen U, Rotter N, et al. A randomized trial of icatibant in ACE-inhibitor-induced angioedema. N Engl J Med. 2015;372:418–25. A multicenter, double blind, randomized phase 2 trial demonstrated that time to complete resolution of edema in patients with ACE-I induced angioedema was shorter with icatibant as compared to combination therapy with glucocorticoids and antihistamines.
49. Sinert R, Levy P, Bernstein JA, Body R, Sivilotti MLA, Moellman J, et al. Randomized trial of Icatibant for angiotensin-converting enzyme inhibitor-induced upper airway angioedema. J Allergy Clin Immunol Pract. 2017;5:1402–3.
50. Lewis LM, Graffeo C, Crosley P, Klausner HA, Clark CL, Frank A, et al. Ecallantide for the acute treatment of angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter, randomized, controlled trial. Ann Emerg Med. 2015;65:204–13.
51. Moellman JJ, Bernstein JA, Lindsell C, Banerji A, Busse PJ, Camargo CA Jr, et al. A consensus parameter for the evaluation and management of angioedema in the emergency department. Acad Emerg Med. 2014;21:469–84.
52. • Zuraw BL, Bernstein JA, Lang DM, Craig T, Dreyfus D, Hsieh F, et al. A focused parameter update: hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema. J Allergy Clin Immunol. 2013;131:1491–1493.e25. A comprehensive update published in 2013 outlining guidelines and recommendations for the management of angioedema resulting from hereditary causes, C1 inhibitor deficiency or secondary to ACE-I use.
53. Erickson DL, Coop CA. Angiotensin-converting enzyme inhibitor-associated angioedema treated with c1-esterase inhibitor: a case report and review of the literature. Allergy Rhinol (Providence). 2016;7:168–71.
54. • Adebayo O, Wilkerson RG. Angiotensin-converting enzyme inhibitor–induced angioedema worsened with fresh frozen plasma. Am J Emerg Med. 2017;35:192.e1–2. An interesting case bringing to light the controversy of risk vs. benefit involving the use of FFP in the treatment of ACE-I induced angioedema.
55. Lewis LM. Angioedema: etiology, pathophysiology, current and emerging therapies. J Emerg Med. 2013;45:789–96.
56. • Toh S, Reichman ME, Houstoun M, Ross Southworth M, Ding X, Hernandez AF, et al. Comparative risk for angioedema associated with the use of drugs that target the renin-angiotensin-aldosterone system. Arch Intern Med. 2012;172:1582–8. A retrospective, observational, inception cohort study that investigated the risks for angioedema with use of ACE-I, ARBs and aliskiren. It found the risk of angioedema to be three times with use of ACE-I and aliskiren.
57. Parving H-H, Brenner BM, McMurray JJV, de Zeeuw D, Haffner SM, Solomon SD, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med. 2012;367:2204–13.
58. • McMurray JJV, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. Angiotensin–neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004. A double-blind trial demonstrating the superiority of combined angiotensin-neprilysin inhibition as compared to enalapril in terms of reducing the risk of death and hospitalization in patients with heart failure with reduced ejection fraction. The cardiovascular benefit came at the cost of higher fraction of patients suffering from hypotension and angioedema.
59. Kostis JB, Moreyra AE, Kostis WJ. Angioedema with renin angiotensin system drugs and neutral endopeptidase inhibitors. J Am Soc Hypertens. 2016;10:387–9.