Angioedema and anaphylaxis are rare adverse events related to angiotensin-converting enzyme (ACE) inhibitors.1-5
Acquired angioedema related to ACE inhibitors usually localizes to the face, followed by lips, eyelids, tongue, neck, and upper airways.1 ACE inhibitor-induced angioedema has a gradual onset, is nonpruritic, and without rash.5
A 2007 review3 analyzed the medical records of 64 patients seen over a period of 13 years at Northwestern Memorial Hospital who developed at least one episode of angioedema while taking either an ACE inhibitor (n=61) or and angiotensin receptor blocker (ARB) (n=3). The study found that the primary location of swelling was the lips and tongue. Urticaria and pruritus were rare, occurring in only two patients. Twenty percent of patients were admitted to the intensive care unit. Time from initiation of therapy to development of angioedema was one month in 25% of patients with 1.8 years as the mean time to onset in the remainder of patients.
A 2003 meta-analysis4 of 354 randomized double-blind placebo-controlled trials of hypertension treatment with thiazides, beta blockers, ARBs, calcium channel blockers, and ACE inhibitors looked at the rate of side effects at the standard dose. A review of studies found that angioedema affects between 1 and 10 per 10,000 patients treated with ACE inhibitors.
The Omapatrilat Cardiovascular Treatment Assessment Versus Enalapril trial, which randomized 12,634 patients to enalapril treatment, found the incidence of angioedema was 0.68%.6
A 2012 meta-analysis of 26 randomized trials (n=74,875) reported an incidence of 0.3% of ACE inhibitor-induced angioedema (95% confidence interval [CI] [0.28 – 0.32]) of ACE inhibitor-induced angioedema compared to 0.07% with placebo (95% CI [0.05 – 0.09]).2 The risk of angioedema with ACE inhibitor therapy was 2.8 times higher than with placebo (95% CI [1.63 – 4.79], p=0.0002) in the ten trials that compare ACE inhibitors (n=19480) and placebos (n=19493) head-to-head.
Based on the 2012 analysis, the 2014 consensus report from the Hereditary Angioedema International Working Group on the classification, diagnosis, and treatment for angioedema concluded that an ACE inhibitor-related angioedema should be classified as a specific form of angioedema.1
Manufacturers recommend that patients with any signs or symptoms suggesting angioedema (swelling of face, extremities, eyes, lips, tongue, difficulty in swallowing or breathing) should stop taking the drug until they have consulted with their doctor.7-16 Angioedema usually resolves with discontinuation of the ACE inhibitor, but in some cases emergency medical treatment may be needed.
References
- Cicardi M, Aberer W, Banerji A, et al. Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group. Allergy 2014; 69 (5): 602-616.
- Makani H, Messerli FH, Romero J, et al. Meta-analysis of randomized trials of angioedema as an adverse event of renin-angiotensin system inhibitors. Am J Cardiol 2012; 110 (3): 383-391.
- Malde B, Regalado J, Greenberger PA. Investigation of angioedema associated with the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Ann Allergy Asthma Immunol 2007; 98 (1): 57-63.
- Law M, Wald N, Morris J. Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy. Health Technol Assess 2003; 7 (31): 1-94.
- Bezalel S, Mahlab-Guri K, Asher I, Werner B, Sthoeger ZM. Angiotensin-converting enzyme inhibitor-induced angioedema. Am J Med 2015; 128 (2): 120-125.
- Kostis JB, Kim HJ, Rusnak J, et al. Incidence and characteristics of angioedema associated with enalapril. Arch Intern Med 2005; 165 (14): 1637-1642.
- Accupril [package insert]. New York, NY: Parke Davis, Pfizer; 2017.
- Capoten [package insert]. Spring Valley, NY: Par Pharmaceutical Companies, Inc.; 2012.
- Vasotec [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; 2015.
- Lotensin [package insert]. Parsippany, NJ: Validus Pharmaceuticals LLC; 2014.
- Altace [package insert]. New York, NY: Pfizer Laboratories; 2017.
- Aceon [package insert]. North Chicago, IL: Abbot Laboratories; 2011.
- Moexipril hydrochloride [package insert]. Teva Pharmaceuticals USA Inc; 2016.
- Fosinopril sodium [package insert]. Miami, FL: Ciplo USA Inc; 2015.
- Trandolapril [package insert]. Laurelton, NY: Epic Pharma, LLC; 2017.
- Prinivil [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2016.
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