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Spironolactone Use in Practice: Risk for Hyperkalemia?

In the RALES randomized, placebo-controlled trial, 25 mg daily of the aldosterone antagonist spironolactone significantly reduced mortality risk among patients with severe heart failure and left-ventricular systolic dysfunction (N Engl J Med 1999; 341:709). Spironolactone is a potassium-sparing diuretic that can cause hyperkalemia, especially at higher doses and in patients with renal dysfunction. RALES subjects rarely experienced hyperkalemia, but some experts have raised concerns about applying the RALES findings in practice. To address this issue, researchers used medical-records databases in Ontario to study rates of spironolactone use and rates of hyperkalemia-related hospitalization before and after RALES was published in 1999.

Spironolactone use remained relatively constant from 1994 through early 1999 but then increased 5-fold after RALES was published. Patients who were taking both ACE inhibitors and spironolactone after RALES were a mean of 13 years older than the trial participants had been. The median dosage of spironolactone used after RALES was 25 mg daily.

Admission rates for hyperkalemia rose slightly from 1994 (2.4 per 1000) to early 1999 (4.0 per 1000). By 2001, the rate had spiked up to 11.0 per 1000. However, heart-failure hospitalizations did not change significantly after 1999. Adjustment for changes in patterns of use of other drugs did not alter the findings.

Comment: This study illustrates the challenge of translating trial findings into practice. The editorialists suggest that higher doses of spironolactone and treatment of patients with renal dysfunction might explain the higher rates of hyperkalemia in practice than in the RALES trial. They emphasize that, used properly, spironolactone has the potential to reduce mortality risk substantially.

— Harlan M. Krumholz, MD, SM

Published in Journal Watch Cardiology December 31, 2004

Citation(s):

Juurlink DN et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med 2004 Aug 5; 351:543-51.

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• Medline abstract (Free)

McMurray JJV and O'Meara E. Treatment of heart failure with spironolactone -- Trial and tribulations. N Engl J Med 2004 Aug 5; 351:526-8.

• Original article (Subscription may be required)
• Medline abstract (Free)