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The Pharmaceutical Journal Vol 263 No 7073 p858
November 27, 1999 Letters

Elite II

Caution required

From Mr A. R. Cox, MRPharmS

SIR,—The announcement that ELITE II shows no significant difference between losartan and captopril in reducing mortality in patients with heart failure is good news for those who cannot tolerate ACE inhibitors. Professor Philip Poole-Wilson states, "If an ACE inhibitor cannot be used for whatever reason, I think that there is a reasonable medical view that it would be appropriate to consider losartan as a treatment in those patients" (PJ, November 20, p812).
This view however may not apply to all patients, in particular those intolerant of ACE inhibitors due to angioedema. Angioedema is a well-defined, non pitting, erythematous oedema of the skin and subcutaneous tissues commonly involving the tongue, lips and eyelids. The soft tissue swelling can be life-threatening. Angioedema is a recognised rare adverse effect of ACE inhibitors. The frequency of angioedema with ACE inhibitors is thought to be 0.1-0.2 per cent.1,2
The precise mechanism of this adverse drug reaction is not known, although it has been postulated that the inhibition of breakdown of bradykinin by ACE inhibitors may be responsible. As angiotensin II receptor antagonists do not inhibit bradykinin breakdown, it had been suggested that angioedema would not occur with these agents. However, there are reports of angioedema associated with angiotensin II receptor antagonists in the literature,3–5 including some in patients who have also experienced angioedema during prior exposure to ACE inhibitors.5–9
The mechanism by which these agents produce angioedema is therefore uncertain. Given the severity of the potential adverse drug reaction, angiotensin II receptor antagonists should be used with caution in patients who have suffered angioedema secondary to ACE inhibition, if at all.
Pharmacists and physicians should be alert to this adverse reaction, which can occur within 24 hours but has been known to present more than a year after commencement of therapy.5,10 Patients should be advised that swelling in the area of the mouth and throat is a possible adverse reaction of angiotensin II receptor antagonists and ACE inhibitors. If any such swelling occurs they should be advised to contact their doctor immediately.

Anthony Cox
Senior Clinical Pharmacist, City Hospital NHS Trust

References

1. Israili ZH, Hall WD. Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy: a review of the literature and pathophysiology. Ann Int Med 1992;117;234-42.
2. Slater EE, Merilll DD, Guess HA, et al. Clinical profile of angioedema associated with angiotensin converting enzyme inhibition. JAMA 1988;260:967-70.
3. Ackerman CG, Greenberg A. Angioedema induced by the angiotensin II blocker losartan (letter). N Engl J Med 1995;333:1572.
4. Rivera JO. Losarten-induced Angioedema. Ann Pharmacother 1999;33:933-5.
5. Rijnsoever EW, Kwee-Zuiderwijk WJM, Feenstra J. Angioneurotic edema attributed to the use of losartan. Arch Intern Med 1998;158:2063-5.
6. Boxer M. Accupril and Cozaar-induced angioedema in the same patient (letter). J Allergy Clin Immunol 1996:98:471.
7. Frye CB, Pettigrew TJ. Angioedema and photosensitivity rash induced by valsartan. Pharmacotherapy 1998: 18:866-8.
8. Cha YJ, Pearson VE. Angioedema due to losartan. Ann Pharmacother 1999;33: 936-8.
9. Sharma PK, Yium JJ. Angioedema associated with angiotensin II receptor antagonist losartan. South Med J 1997;90:552-3.
10. Pylypchuk GB. ACE inhibitor versus angiotensin II blocker-induced cough and angioedema. Ann Pharmacother 1998;32:1060-6.