Incidence and Predictors of Hyperkalemia in Patients With Heart Failure
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Objectives We explored the incidence and predictors of hyperkalemia in a broad population of heart failure patients.Background When used in optimal doses to treat patients with heart failure, renin-angiotensin-aldosterone system (RAAS) inhibitors improve clinical outcomes but can cause hyperkalemia.Methods Participants in the CHARM (Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity) (n = 7,599) Program were randomized to standard heart failure therapy plus candesartan or placebo, titrated as tolerated to a target of 32 mg once daily with recommended monitoring of serum potassium and creatinine. We assessed the incidence and predictors of hyperkalemia associated with dose reduction, study drug discontinuation, hospitalization, or death over the median 3.2 years of follow-up.Results Independent of treatment assignment, the risk of hyperkalemia increased with age > or =75 years, male gender, diabetes, creatinine > or =2.0 mg/dl, K+ > or =5.0 mmol/l, and background use of angiotensin-converting enzyme inhibitors or spironolactone. Candesartan increased the rate of aggregate hyperkalemia from 1.8% to 5.2% (difference 3.4%, p < 0.0001) and serious hyperkalemia (associated with death or hospitalization) from 1.1% to 1.8% (difference 0.7%, p < 0.001), with hyperkalemia associated with death reported in 2 (0.05%) candesartan patients and 1 (0.03%) placebo patient. The benefit of candesartan in reducing cardiovascular death or heart failure hospitalization (relative risk reduction 16%, p < 0.0001) was uniform in these subgroups, as was the incremental risk of hyperkalemia.Conclusions The risk of hyperkalemia is increased in symptomatic heart failure patients with advanced age, male gender, baseline hyperkalemia, renal failure, diabetes, or combined RAAS blockade. Although these groups derive incremental clinical benefit from candesartan, careful surveillance of serum potassium and creatinine is particularly important.
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In the overall CHARM program, patients with T2DM had double the risk of developing hyperkalaemia on candesartan compared to those without T2DM.
“In the overall CHARM program, patients with T2DM had double the risk of developing hyperkalaemia on candesartan compared to those without T2DM.147”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [147]
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- Authors
- Desai, A. S., Swedberg, K., McMurray, J. J. V., Granger, C. B., Yusuf, S., Young, J. B., Dunlap, M. E., Solomon, S. D., Hainer, J. W., Olofsson, B., Michelson, E. L., & Pfeffer, M. A.
- Affiliations
- Brigham and Women's Hospital (US)
- University of Gothenburg (SE)
- Western Infirmary (GB)
- Duke Medical Center (US)
- Cleveland Clinic (US)
- Case Western Reserve University (US)
- AstraZeneca (United States) (US)
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2007-11
- Volume
- 50
- Issue
- 20
- Pages
- 1959-1966
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W170303893
- Cited by
- 170
- References
- 21
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 9 · 2023: 5 · 2022: 5 · 2021: 11 · 2020: 2 · 2019: 13 · 2018: 14 · 2017: 13 · 2016: 8 · 2015: 4 · 2014: 9 · 2013: 9 · 2012: 15
- FWCI
- 8.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (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, heart failure, candesartan, renin-angiotensin-aldosterone system inhibitors, risk factors, serum potassium monitoring, renal failure, diabetes mellitus, spironolactone, ACE inhibitors, drug safety, cardiovascular mortality
- MeSH terms
- Aged, Aged, 80 and over, Benzimidazoles, Biphenyl Compounds, Female, Follow-Up Studies, Heart Failure, Humans, Hyperkalemia, Male, Predictive Value of Tests, Retrospective Studies, Risk Factors, Tetrazoles, Incidence, Angiotensin II Type 1 Receptor Blockers
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