Spironolactone treatment is associated with better cardiovascular outcomes but increased risk of hyperkalemia among patients with chronic kidney disease (CKD) who have heart failure with preserved ejection fraction (HFpEF), new study findings suggest.

In a post-hoc analysis of data from 1767 participants in the Americas region of the TOPCAT (Treatment of Preserved Cardiac Function heart Failure With an Aldosterone Antagonist Trial) trial, a team led by Akshay S. Desai, MD, of Brigham and Women’s Hospital in Boston, found that spironolactone-treated patients had a lower risk of the primary efficacy outcome—a composite of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest—compared with placebo recipients across all categories of estimated glomerular filtration rate (eGFR).

Overall, spironolactone decreased the risk of the primary outcome by 12% compared with placebo, Dr Desai and colleagues reported in JACC: Heart Failure. The decrease in risk was significantly greater only among patients with an eGFR (in mL/min/1.73 m2) of 60 or above. In this group, spironolactone decreased the risk of the primary outcome by 34%.

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Spironolactone, however, increased the absolute risk of worsening renal function (doubling of serum creatinine values) and hyperkalemia (serum potassium level above 5.5 mmol/L).

The incidence of hyperkalemia increased with decreasing renal function in both the spironolactone and placebo groups, but the incidence was significantly greater among spironolactone-treated patients across ranges of eGFR. The incidence in the spironolactone and placebo groups was 6.8 and 1.4 per 100 patient-years, respectively, among patients with an eGFR of 60 or higher, 11.9 and 3.6 per 100 patient-years among patients with an eGFR of 45 to 60, and 14.7 and 5.3 per 100 patient-years among those with an eGFR below 45.

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“These data support the potential benefits of spironolactone in patients with HFpEF and low eGFR, but emphasize the imperative for careful surveillance to limit the risk of drug-related AEs,” the authors wrote.

The TOPCAT trial was an international study of spironolactone that included 3445 patients with symptomatic HFpEF. Investigators randomly assigned patients to receive spironolactone or placebo over a mean follow-up duration of 3.3 years.


Beldhuis IE, Myhre PL, Claggett B, et al. Efficacy and safety of spironolactone in patients with HFpEF and chronic kidney disease. JACC Heart Fail. 2019;7:25-32.