Angioedema Associated With Angiotensin-Converting Enzyme Inhibitor Use

Abstract

A 71-year-old woman presented with a sudden onset of shortness of breath and difficulty speaking. She was a former smoker and had no known allergies. During assessment, she experienced periorbital swelling without pruritus (Figure 1). She was immediately given antihistamine and cortisone treatment, and the swelling slowly resolved and her speech improved. On further enquiry, we found that she had been taking acetylsalicylic acid (ASA) and bisoprolol for hypertension and coronary artery disease for about 10 years, but she had started coughing after perindopril had been added to her medication several days earlier. We believed that perindopril alone or in combination with ASA was the most likely cause of the angioedema, and we changed her medication to amlodipine and clopidogrel. 1 During three months of follow-up, neither angioedema nor cough recurred, and the laboratory results were not indicative of hereditary angioedema. Adverse reactions after short-and long-term intake of angiotensin-converting enzyme (ACE) inhibitors alone or in combination with ASA are common. 1-3 Of those who use ACE inhibitors, angioedema occurs in about 0.5% of white people and up to 5% of black people. 1 About one-quarter of episodes occur during the first month of therapy. 1 There are no known modifiable risk factors, but the risk appears to be higher for women than men and those with C1 esterase inhibitor deficiency, as well as for people of black and Asian descent. 1,4 A history of asthma or urticaria may also be associated with increased risk, especially in combination with ASA use. 1 After acute treatment of angioedema associated with the use of ACE inhibitors, experts recommend immediate discontinuation of the drug and strict lifetime avoidance of this class of medication. 1-3 Although switching to an angiotensin-receptor blocker may improve ACE inhibitor-associated coughing, 1-3 the high cross-reactivity (up to 17%) between ACE inhibitors and angiotensin-receptor blockers may put those with previous episodes of ACE inhibitor-mediated angioedema at increased risk of further occurrences. 2,3 Clinicians should avoid both classes of drugs for patients susceptible to ACE inhibitor-mediated angioedema to prevent potentially life-threatening complications. 2,3 References 1. Vasekar M, Craig TJ. ACE inhibitor-induced angioedema. Curr Allergy Asthma Rep 2012;12:72-8. 2. Beavers CJ, Dunn SP, Macaulay TE. The role of angiotensin receptor blockers in patients with angiotensin-converting enzyme inhibitor-induced angioedema. Ann Pharmacother 2011; 45:520-4. 3. Kanani A, Schellenberg R, Warrington R. Urticaria and angioedema. Allergy Asthma Clin Immunol 2011;7(Suppl 1):S9. 4. Hoover T, Lippmann M, Grouzmann E, et al. Angiotensin converting enzyme inhibitor induced angio-oedema: a review of the pathophysiology and risk factors. Figure 1: Several days after starting perindopril, a 71-year-old woman experienced shortness of breath and periorbital edema. She was also taking acetyl-salicylic acid and bisoprolol.

Increased Incidence of Angioedema with ACE Inhibitors in Combination with mTOR Inhibitors in Kidney Transplant Recipients

“…In a small series, only 2 of 26 patients with ACEi-induced angioedema developed angioedema after conversion to ARBs. Thus, conversion to ARBs has been recommended as an overall safe option in patients with ACEi-induced angioedema, which is supported by our own experience and most sirolimus-associated cases described in the literature (7).…”

Brief review: Angiotensin converting enzyme inhibitors and angioedema: anesthetic implications

“…85,94 Stopping the ACEI provides a successful measure in the majority of patients who develop ACEI-related angioedema, 94 and is considered the next most important step in management, after ensuring patency of the patient's airway. However, failure to recognize the association of ACEI drugs with this condition is common, and not infrequently the offending agent is continued upon discharge from hospital.…”

“…80 Recent data suggest that the majority of patients who develop angioedema from ACEI drugs can tolerate angiotensin-II receptor blockers (ARB). 94,97 Angiotensin II receptor antagonists act at the receptor sites and do not affect the angiotensin converting enzyme; hence, theoretically, bradykinin levels should remain unaffected. However, sporadic case reports have described angioedema related to angiotensin II receptor blockers, and it is important for clinicians to be aware that ARBs may not be safe alternatives in patients with ACEI related angioedema.…”

“…However, sporadic case reports have described angioedema related to angiotensin II receptor blockers, and it is important for clinicians to be aware that ARBs may not be safe alternatives in patients with ACEI related angioedema. 94,[98][99][100] In 32% of reported cases of angioedema related to ARB, patients experienced a prior episode of angioedema attributable to ACEI therapy.…”

About a Case of Neurotic Angioedema Induced by Angiotensin Converting Enzyme Inhibitor

“…Bradykinin. The accumulation of bradykinin increases the vascular permeability responsible for the formation of edema if the aminopeptidase P activity is insufficient [12] [17].…”