Abstract
Background
Spironolactone reduces morbidity and mortality in patients with heart failure (HF) with reduced ejection fraction (EF) and decreases hospitalizations in HF with preserved EF. To minimize the risk of hyperkalemia, patients must have an estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2 and potassium < 5.0 mEq/L prior to initiation; however, spironolactone is prescribed outside these parameters. The objective of this study was to evaluate the safety and tolerability of spironolactone in patients with HF and chronic kidney disease (CKD).
Methods
This single-center, retrospective cohort study evaluated patients ≥ 18 years with HF and CKD stages 3–5 who received ≥ 48 h of spironolactone therapy and were hospitalized from February 2018 to August 2019. The primary outcome was incidence of hyperkalemia (potassium ≥ 5.5 mEq/L).
Results
Overall, 121 patients were evaluated: 52.1% (n = 63) had an EF > 40% and 47.9% (n = 58) had an EF ≤ 40% with 69.4% (n = 84) CKD stage 3, 24.8% (n = 30) stage 4, and 5.8% (n = 7) stage 5. Spironolactone was initiated prior to admission (PTA) for 54.5% (n = 66) of patients, while 45.5% (n = 55) of orders were initiated during hospitalization. Eight patients (6.6%) experienced inpatient hyperkalemia—all with PTA spironolactone. Patients who experienced inpatient hyperkalemia had a numerically lower eGFR that was not statistically significant (35.40 vs. 38.22 mL/min/1.73 m2; p = 0.730). Patients with CKD stage 3 (n = 4) had numerically higher rates of inpatient hyperkalemia than stages 4 (n = 1) or 5 (n = 3) (50%, 12.5%, and 37.5% respectively; p < 0.05).
Conclusion
Spironolactone may be safe to initiate in hospitalized patients with HF and CKD; however, appropriateness of therapy must be assessed upon admission to the hospital. Larger studies are needed for conclusive results.
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This manuscript has been read and approved by all study authors, and the 4 criteria for authorship have been met. The authors all made substantial contributions to design, analysis, and interpretation of this study, its revisions, and final approval. All authors agree to being accountable for all parts of the study, and this manuscript represents honest work carried out by the study authors as detailed above.
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Amanda Buckallew, Rachel Watson, William Miller, Gina Mbachu, Cameron Whitlock, Jay Seltzer, and Anastasia Armbruster do not have anything to disclose concerning possible financial or personal relationships with commercial entities that may have a direct or indirect interest in the subject matter of this manuscript. Katie Tellor was employed at St. Louis College of Pharmacy when the research was conducted and analyzed, and during the initial drafting of the manuscript. She is currently an employee and stockholder of Pfizer, Inc. and contributed to the final approval of the current version during her employment.
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Buckallew, A.R., Tellor, K.B., Watson, R. et al. Evaluation of the safety and tolerability of spironolactone in patients with heart failure and chronic kidney disease. Eur J Clin Pharmacol 77, 955–960 (2021). https://doi.org/10.1007/s00228-020-03069-7
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DOI: https://doi.org/10.1007/s00228-020-03069-7