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Clinical Review Lesson of the week

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

BMJ 2003; 327 doi: (Published 17 July 2003) Cite this as: BMJ 2003;327:147
  1. Eike Wrenger, nephrologist (,
  2. Regina Müller, internist1,
  3. Michael Moesenthin, nephrologist1,
  4. Tobias Welte, intensive care physician2,
  5. Jürgen C Frölich, professor of clinical pharmacology3,
  6. Klaus H Neumann, professor of nephrology1
  1. 1Division of Nephrology, Department of Internal Medicine, Otto-von-Guericke-University, Leipziger Strasse 44, D-39120 Magdeburg, Germany
  2. 2Division of Cardiology, Pulmonology, and Angiology, Department of Internal Medicine, Otto-von-Guericke-University
  3. 3Institute of Clinical Pharmacology, Medizinische Hochschule, Hannover, Germany
  1. Correspondence to: E H Wrenger
  • Accepted 17 April 2003


The randomised aldactone evaluation study (RALES) proved a substantial (30%) reduction in risk of mortality in patients with severe congestive heart failure by treatment with low dose spironolactone (25-50 mg a day) in addition to standard treatment.1 Exclusion criteria for treatment in the study were a plasma potassium concentration > 5.0 mmol/l and serum creatinine concentration > 221 μmol/l. A pilot study had previously shown that the higher the dosage of spironolactone (up to 24% with 75 mg a day) the higher the risk of hyperkalaemia.2 Standard treatment for patients with heart failure categorised as New York Heart Association class II to IV includes angiotensin converting enzyme (ACE) inhibitors or angiotensin II AT1 receptor antagonists (AT1 receptor blockers).3 Both spironolactone and ACE inhibitors or AT1 receptor blockers reduce the renal elimination of potassium.4 In RALES, the increase in potassium was judged not to be important as serious hyperkalaemia (> 6 mmol/l) occurred in only 10 (1%) of 841 patients taking placebo and in 14 (2%) of 822 patients taking spironolactone, with no significant difference between the groups. Discontinuation of the treatment was necessary in only one patient taking placebo and three patients taking spironolactone.1

We present a larger case series of life threatening hyperkalaemia in patients who were receiving spironolactone plus ACE inhibitors or AT1 receptor blockers. We identify clinical circumstances associated with this medical emergency and suggest recommendations for prevention.

Case series

From January 1999 until December 2002 we observed 44 patients (17 men) with congestive heart failure who were taking spironolactone and ACE inhibitors or AT1 receptor blockers and were admitted to our nephrology unit …

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