Efficacy and Safety of Spironolactone in Patients With HFpEF and Chronic Kidney Disease

Iris E. Beldhuis, Peder L. Myhre, Brian Claggett, Kevin Damman, James C. Fang, Eldrin F. Lewis, Eileen O'Meara, Bertram Pitt, Sanjiv J. Shah, Adriaan A. Voors, Marc A. Pfeffer, Scott D. Solomon, Akshay S. Desai*

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Objectives: This study investigated the association between baseline renal function and the net benefit of spironolactone in patients with heart failure (HF) with a preserved ejection fraction (HFpEF). Background: Guidelines recommend consideration of spironolactone to reduce HF hospitalization in HFpEF. However, spironolactone may increase risk for hyperkalemia and worsening renal function, particularly in patients with chronic kidney disease. Methods: This investigation analyzed data from patients enrolled in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial) Americas study (N = 1,767) to examine the association between the baseline estimated glomerular filtration rate (eGFR) and the primary composite outcome of cardiovascular death, HF hospitalization, or aborted cardiac arrest, as well as safety outcomes, including hyperkalemia, worsening renal function, and permanent drug discontinuation for adverse events (AEs). Variations in the efficacy and safety of spironolactone according to eGFR were examined in Cox models using interaction terms. Results: The incidence of both the primary outcome and drug-related AEs increased with declining eGFR. Compared with placebo, across all eGFR categories, spironolactone was associated with lower relative risk for the primary efficacy outcome and for hypokalemia, but higher relative risk for hyperkalemia, worsening renal function, and drug discontinuation. During 4-year follow-up, the absolute risk for AEs that prompted drug discontinuation was amplified in the lower eGFR categories, which suggested heightened risk for drug intolerance with declining renal function. Conclusions: Although consistent efficacy of spironolactone was observed across the range of eGFR, the risk of AEs was amplified in the lower eGFR categories. These data supported use of spironolactone to treat HFpEF patients with advanced chronic kidney disease only when close laboratory surveillance is possible.

Original languageEnglish (US)
Pages (from-to)25-32
Number of pages8
JournalJACC: Heart Failure
Volume7
Issue number1
DOIs
StatePublished - Jan 2019

Keywords

  • chronic kidney disease
  • heart failure with preserved ejection fraction
  • renal function
  • safety
  • spironolactone

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Beldhuis, I. E., Myhre, P. L., Claggett, B., Damman, K., Fang, J. C., Lewis, E. F., O'Meara, E., Pitt, B., Shah, S. J., Voors, A. A., Pfeffer, M. A., Solomon, S. D., & Desai, A. S. (2019). Efficacy and Safety of Spironolactone in Patients With HFpEF and Chronic Kidney Disease. JACC: Heart Failure, 7(1), 25-32. https://doi.org/10.1016/j.jchf.2018.10.017