Spironolactone use and renal toxicity: population based longitudinal analysis.

Objective: To determine the safety of spironolactone prescribing in the setting of the UK National Health Service.

Design: Population based longitudinal analysis using a record linkage database.

Setting: Tayside, Scotland. Population All patients who received one or more dispensed prescriptions for spironolactone between 1994 and 2007.

Main Outcome Measures: Rates of prescribing for spironolactone, hospital admissions for hyperkalaemia, and hyperkalaemia and renal function without admission, before and after the publication of results from the Randomised Aldactone Evaluation Study (RALES).

Results: Prescriptions for spironolactone and measurements of serum creatinine and serum potassium all increased in parallel in Tayside after the release of the RALES results in 1999 (from 2847, 5345, and 5246 in the first half of 1999 to 6582, 10,753, and 10,534 by the second half of 2001, and to 8619, 17,844, and 17,649 by 2007). These increases occurred in patients with and without heart failure. Few hospital admissions for hyperkalaemia occurred over this time: three in the first quarter of 1995, two in the last quarter of 2001, and three in 2007. Among patients who were taking angiotensin converting enzyme inhibitors and who had recently been admitted to hospital for heart failure, the rate of spironolactone use was 19.8 per 100 patients in early 1999 rising to 70.1 per 100 patients by late 2001 (P<0.01) and 61.3 by 2007. The rate of outpatient measured hyperkalaemia (serum K(+)>6 mmol/l) did not increase over time (9.9 per 100 patients in early 1999, 6.9 per 100 patients in late 2001, and 2.9 per 100 patients in 2007) despite the increased use of spironolactone.

Conclusions: Despite a marked increased in the use of spironolactone in patients with and without heart failure, no increase was seen in hospital admissions for hyperkalaemia and outpatient hyperkalaemia actually fell. Careful monitoring of patients prescribed spironolactone seems to have been associated with no increase in risk of hyperkalaemia.