The use of spironolactone (Aldactone) therapy for heart failure increased more than sevenfold after the publication of the Randomized ALdactone Evaluation Study (RALES). The RALES inclusion criteria outlined specific treatment parameters for spironolactone therapy in patients with left ventricular systolic dysfunction and subsequent heart failure, which are similar to current guidelines (see accompanying table). Although RALES showed a decrease in mortality and hospitalization in patients who met these parameters, spironolactone therapy may cause serious hyperkalemia in patients with marginal renal function, relatively high baseline potassium levels, or type IV renal tubular acidosis. It is important to note that RALES excluded patients at high risk of hyperkalemia because of renal insufficiency or diabetes, and patients were under strict surveillance for increasing potassium levels and worsening kidney function. These exclusions and continual monitoring do not reflect usual clinical practice, and there is significant concern about the safety of current treatment patterns of spironolactone use in the community-based population, particularly in patients with noncardiovascular comorbidities. Masoudi and colleagues studied spironolactone prescription rates after RALES in patients who do not meet the RALES criteria and the resultant complications.

The authors used data from the National Heart Care Project, an ongoing initiative funded by Medicare and Medicaid to improve the quality of care for Medicare beneficiaries hospitalized with a principal diagnosis of heart failure. Two cohorts (one from 1998 to 1999 and the other from 2000 to 2001) with a combined population of 19,226 patients were selected. Inclusion criteria were age of 65 years or older and ejection fraction less than 40 percent. The final patient population included mostly men with a history of hypertension, coronary artery disease, diabetes, or chronic pulmonary disease.

The study showed that 30.9 percent of patients who did not meet the RALES criteria received spironolactone. Hyperkalemic-related hospitalizations and mortality increased as well. These increases also occurred in Canada, where spironolactone use increased from 3.4 to 14.9 percent with a subsequent increase in hyperkalemia-related hospitalizations and mortality.

The authors conclude that the increase in hyperkalemic morbidities associated with increasing spironolactone use after RALES suggests the need for change in the current patterns of aldosterone-blocking drug use. However, RALES showed that the use of spironolactone in patients who meet the study’s criteria improves morbidity and mortality.