Angioedema and anaphylaxis are very rare adverse events related to angiotensin receptor blockers (ARBs).1-3
Acquired angioedema related to angiotensin-converting enzyme inhibitors (ACEIs) usually localizes to the face, followed by lips, eyelids, tongue, neck, and upper airways.1 Angioedema developing in people taking ARBs has been reported, but with significantly less frequency than with ACEIs.3-9 A 2007 review analyzed the medical records of 64 patients seen over a period of 13 years at one hospital who developed at least one episode of angioedema while taking either an ACEI (n=61) or an ARB (n=3).3 The study found that the primary location of swelling was the lips and tongue and urticaria and pruritus were rare occurring in only two patients. 20% of patients were admitted to the intensive care unit. Time from beginning 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 2012 meta-analysis of randomized trials of angioedema as an adverse event of renin-angiotensin system inhibitors examined 19 trials with 35,479 patients on ARBs.2 The weighted incidence of angioedema with ARBs was 0.11% (95% confidence interval [CI] [0.09 – 0.13]) as compared to 0.30% (95% CI [0.28 – 0.32]) with ACEIs. The incidence of angioedema with ARBs was not significantly different than that of placebo. The incidence was higher in people with heart failure than those without heart failure.
Some experts recommend caution when prescribing an ARB to someone who previously had ACEI-related angioedema. A 2000 review of case reports of people who developed angioedema on an ARB found that 32% of these patients previously had angioedema while taking an ACEI.1
Based on the previous analysis, the 2014 consensus report from the Hereditary Angioedema International Working Group on the classification, diagnosis, and treatment for angioedema concluded that an ARB-related angioedema should not be included as a specific form of angioedema, whereas ACEI-angioedema is a specific form.1
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.
- Acker CG, Greenberg A. Angioedema induced by the angiotensin II blocker losartan. N Engl J Med 1995; 333 (23): 1572.
- Wilson M, Frohna W, Trent G, Sauter D. Evaluating for seasonal variation in angiotensin-converting enzyme inhibitor- and angiotensin receptor blocker-induced angioedema. Ann Allergy Asthma Immunol 2014; 112 (2): 178-179.
- van Rijnsoever EW, Kwee-Zuiderwijk WJ, Feenstra J. Angioneurotic edema attributed to the use of losartan. Arch Intern Med 1998; 158 (18): 2063-2065.
- Biswas PN, Wilton LV, Shakir SW. The safety of valsartan: results of a postmarketing surveillance study on 12881 patients in England. J Hum Hypertens 2002; 16 (11): 795-803.
- Cozaar [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; 2015.
- Nielsen EW. Hypotensive shock and angio-oedema from angiotensin II receptor blocker: a class effect in spite of tripled tryptase values. J Intern Med 2005; 258 (4): 385-387.
- Warner KK, Visconti JA, Tschampel MM. Angiotensin II receptor blockers in patients with ACE inhibitor-induced angioedema. Ann Pharmacother 2000; 34 (4): 526-528.
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