Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study
Open accessAbstract
Background The Randomized Aldactone Evaluation Study (RALES) demonstrated that spironolactone significantly improves outcomes in patients with severe heart failure. Use of angiotensin-converting-enzyme (ACE) inhibitors is also indicated in these patients. However, life-threatening hyperkalemia can occur when these drugs are used together. Methods We conducted a population-based time-series analysis to examine trends in the rate of spironolactone prescriptions and the rate of hospitalization for hyperkalemia in ambulatory patients before and after the publication of RALES. We linked prescription-claims data and hospital-admission records for more than 1.3 million adults 66 years of age or older in Ontario, Canada, for the period from 1994 through 2001. Results Among patients treated with ACE inhibitors who had recently been hospitalized for heart failure, the spironolactone-prescription rate was 34 per 1000 patients in 1994, and it increased immediately after the publication of RALES, to 149 per 1000 patients by late 2001 (P Conclusions The publication of RALES was associated with abrupt increases in the rate of prescriptions for spironolactone and in hyperkalemia-associated morbidity and mortality. Closer laboratory monitoring and more judicious use of spironolactone may reduce the occurrence of this complication.
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These adverse effects along with the report of higher incidence of hyperkalemia after the publication of the Randomized Aldactone Evaluation Study limited the use of these agents in high-risk populations.
“These adverse effects along with the report of higher incidence of hyperkalemia after the publication of the Randomized Aldactone Evaluation Study limited the use of these agents in high-risk populations.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [159]
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Self-citation
- Authors
- Juurlink, D. N., Mamdani, M. M., Lee, D. S., Kopp, A., Austin, P. C., Laupacis, A., & Redelmeier, D. A.
- Affiliations
- University of Toronto (CA)
- Institute for Clinical Evaluative Sciences (CA)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2004-08-05
- Volume
- 351
- Issue
- 6
- Pages
- 543-551
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2111945961
- Cited by
- 1,761
- References
- 2
- Citations by year
- 2026: 47 · 2025: 36 · 2024: 40 · 2023: 58 · 2022: 57 · 2021: 55 · 2020: 54 · 2019: 72 · 2018: 73 · 2017: 67 · 2016: 57 · 2015: 83 · 2014: 97 · 2013: 84 · 2012: 124
- FWCI
- 92.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Potassium and Related Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- hyperkalemia, spironolactone, ACE inhibitors, heart failure, drug-drug interactions, prescribing patterns, hospitalization, mortality, older adults, laboratory monitoring
- MeSH terms
- Adrenergic beta-Antagonists, Aged, Mineralocorticoid Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Drug Therapy, Combination, Drug Utilization, Female, Heart Failure, Hospitalization, Humans, Hyperkalemia, Male, Practice Patterns, Physicians', Drug Prescriptions, Spironolactone, Randomized Controlled Trials as Topic, Adverse Drug Reaction Reporting Systems, Hospital Mortality
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