Complications of inappropriate use of spironolactone in heart failure: when an old medicine spirals out of new guidelines

J Am Coll Cardiol. 2003 Jan 15;41(2):211-4. doi: 10.1016/s0735-1097(02)02694-3.


Objectives: This study was designed to investigate the appropriateness and complications of the use of spironolactone for heart failure (HF) in clinical practice.

Background: Spironolactone was reported by one prospective randomized trial to decrease morbidity and mortality in patients with New York Heart Association (NYHA) class III and IV HF. With this report (Randomized Spironolactone Evaluation Study [RALES] trial), we noted a marked increase in widespread use of spironolactone in patients with HF. Long-term outcome data with respect to safety and utilization of this medication in HF are not available.

Methods: To investigate the use of spironolactone for HF in a clinical setting, we analyzed the application of the RALES trial protocol to the care of 104 patients, whom we identified as being started on spironolactone for HF after prerelease of the RALES trial.

Results: We found broader use, less intensive follow-up, and increased complications with spironolactone treatment compared with the RALES trial. Cardiologists provided more appropriate care than did primary care providers.

Conclusions: These data suggest that spironolactone is being used widely in HF without consideration of the NYHA class and ejection fraction, and without optimization of background treatment with angiotensin-converting enzyme inhibitors and beta-blockers. Clinical follow-up does not adhere to the RALES trial guidelines, resulting in higher complications. We conclude that long-term studies with further safety and efficacy data are needed.

Publication types

  • Clinical Trial
  • Comment
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Guideline Adherence
  • Heart Failure / drug therapy*
  • Humans
  • Hyperkalemia / etiology
  • Hyponatremia / etiology
  • Hypotension / etiology
  • Male
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists / adverse effects*
  • Mineralocorticoid Receptor Antagonists / therapeutic use
  • Patient Selection
  • Practice Guidelines as Topic
  • Randomized Controlled Trials as Topic
  • Severity of Illness Index
  • Spironolactone / adverse effects*
  • Spironolactone / therapeutic use


  • Mineralocorticoid Receptor Antagonists
  • Spironolactone