Correspondence
Angioedema Induced by the Angiotensin II Blocker Losartan
N Engl J Med 1995; 333:1572December 7, 1995
- Article
To the Editor:
Losartan (Cozaar, Merck) is a new, orally effective blocker of the angiotensin II receptor. The currently available angiotensin-converting–enzyme (ACE) inhibitors block the degradation of bradykinin, which is also metabolized by ACE. The accumulation of potent vasodilator kinins is believed to be the cause of cough and angioneurotic edema induced by ACE inhibitors. Because losartan does not have ACE activity, it would not be expected to increase bradykinin levels.1 The drug has therefore been advocated as being potentially free of these adverse effects. However, angioneurotic edema did occur in 1 patient among 4058 treated.1 We report another case of angioneurotic edema after the administration of losartan.
A 52-year-old man with a history of focal segmental glomerulosclerosis was seen for the control of hypertension. He had received a variety of drugs, including captopril, which had been discontinued because of cough. The cough resolved with the cessation of the drug; there was no history of angioedema. The patient was also allergic to radiographic contrast material. His current treatment included bisoprolol–hydrochlorothiazide and terazosin. His blood pressure was 170/105 mm Hg. His physical examination was otherwise unremarkable. The serum creatinine concentration was 1.2 mg per deciliter, and there was proteinuria of 4+. After the discontinuation of bisoprolol–hydrochlorothiazide, a single 50-mg dose of losartan was given. Within 30 minutes, the patient reported a “scratchy throat” and a feeling of something stuck in the throat. Facial flushing and swelling of the lips and the right side of the face were observed. There was no dyspnea, and the pulmonary examination was normal. All the findings resolved after treatment with diphenhydramine.
Treatment with ACE inhibitors has been shown to cause anaphylaxis due to the activation of bradykinin during dialysis with polyacrylonitrile membranes.2 ACE-inhibitor–induced cough is thought to result from the inhibition of bradykinin degradation by ACE inhibitors, with accompanying effects of bradykinin on prostaglandins, leukotrienes, and substance P.3 Losartan causes cough at a frequency equal to that of cough caused by hydrochlorothiazide and less than half that of cough caused by lisinopril.4 Unlike enalapril, losartan does not increase blood flow in the forearm after an infusion of bradykinin.5 If bradykinin causes ACE-inhibitor–induced cough or anaphylaxis, losartan should be nearly free of these side effects.
Together with the previous report by the manufacturer,1 our report of angioedema after losartan treatment suggests that this hypothesis is incorrect. Until more experience with losartan is accumulated, we urge that the drug be used cautiously in patients with a history of sensitivity to ACE inhibitors.
5 ReferencesChristopher G. Acker, M.D.
Arthur Greenberg, M.D.
University of Pittsburgh, Medical Center, Pittsburgh, PA 15213-25001
Cozaar. West Point, Pa.: Merck (package insert).
2
Verresen L ,Fink E ,Lemke H-D ,Vanrenterghem Y . Bradykinin is a mediator of anaphylactoid reactions during hemodialysis with AN69 membranes. Kidney Int 1994;45:1497-1503
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Lacourciere Y ,Lefebvre J ,Nakhle G ,Faison EP ,Snavely DB ,Nelson EB . Association between cough and angiotensin converting inhibitors versus angiotensin II antagonists: the design of a prospective, controlled study. J Hypertens 1994;12:Suppl 2:S49-S53
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Lacourciere Y ,Brunner H , Irwin, R, et al. Effects of modulators of the renin-angiotensin-aldosterone system on cough. J Hypertens 1994;12:1387-1393
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Cockcroft JR ,Sciberras DG ,Goldberg MR ,Ritter JM . Comparison of angiotensin-converting enzyme inhibition with angiotensin II receptor antagonism in the human forearm. J Cardiovasc Pharmacol 1993;22:579-584
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Full Text35
&NA;. (1995) Losartan potassium. Reactions Weekly &NA;:581, 9
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