Interaction of spironolactone with ACE inhibitors or angiotensin receptor blockers: analysis of 44 cases

Wrenger et al have reported severe hyperkalaemia in a series of
patients taking spironolactone in combination with ACE inhibitors or
Angiotensin-II antagonists1. It is likely to be significant that the
prevalence of diabetes in these patients is strikingly high (80%).

In a study of the prevalence of hyperkalaemia in an unselected
diabetic out-patient population we found that hyperkalaemia was relatively
common in patients with both type 1 and type 2 diabetes 2. Of 1764
consecutive patients attending a hospital diabetic clinic over a one year
period, serum potassium concentration was in excess of 5.0 mmol L-1 in 270
patients (15%) and in excess of 5.4 mmol L-1 in 67 patients (4%). Six
patients had a serum potassium greater than 6.0 mmol L-1. In contrast,
only four patients had a serum potassium of less than 3.4 mmol L-1. At the
time of the study a relatively small proportion of patients were receiving
drugs which could increase potassium (20% of patients with hyperkalaemia)
as Angiotensin-II antagonists were not then available, and use of ACE
inhibitors in patients with diabetes was less well established.

These data suggest that diabetes is an independent risk factor for
hyperkalaemia. Dangerous hyperkalaemia following use of ACE inhibitor
drugs and potassium-sparing diuretics are well described in diabetic
patients3, 4 , and the British National Formulary advises caution
prescribing amiloride for diabetic patients. The report of by Wrenger et
al reinforces the concern that patients with diabetes appear to be
particularly sensitive to the hyperkalaemic effect of drugs which block
potassium excretion, particularly when used in combination. Physicians
treating patients with diabetes should be aware of the dangers of
precipitating life-threatening hyperkalaemia when prescribing for their
patients, and the combination of spironolactone with ACE inhibitors or
Angiotensin-II antagonists for heart failure should be used with extreme
caution in diabetic patients.

PR Jarman

National Hospital for Neurology and Neurosurgery,
Queen Square,
London WC1N 3BG

HM Mather

Ealing Hospital,
Uxbridge Rd,
Middlesex UB1 3HW

References:

1. Wrenger E et al. Interaction of spironolactone with ACE inhibitors or
angiotensin receptor blockers: analysis of 44 cases. BMJ 2003;327: 147-9.

2. Jarman PR, Kehley AM, Mather HM. Hyperkalaemia in diabetes: prevalence
and associations. Postgrad Med J 1995; 71: 551-2.

3. Odawara M, Asano M, Yamashita K. Life-threatening hyperkalaemia
caused by angiotensin-converting enzyme-inhibitor and diuretics. Diabetic
Med 1997; 14: 169-170.

4. Walmsley RN, White GH, Cain M, McCarthy PJ, Booth J. Hyperkalaemia in
the elderly. Clinical chemistry 1984; 30: 1409-1412.

Competing interests:  
None declared