Determination of serum concentrations of canrenone (active metabolite of spironolactone) in patients with heart failure with reduced ejection fraction: a cross-sectional study.

BACKGROUND: Serum canrenone concentrations have so far only been measured in patients with acute heart failure or heart failure with preserved ejection fraction. The results of these studies showed that low or undetectable canrenone concentrations could contribute to the lack of pharmacological effect of spironolactone, while patients with detectable canrenone concentrations had significantly higher potassium concentrations. However, no detailed information on serum canrenone concentrations in patients with heart failure with reduced ejection fraction (HFrEF) has been published to date. The aim of the study was to determine serum canrenone concentrations in samples collected from patients with HFrEF during routine medical care and correlate them with selected clinical parameters such as left ventricular ejection fraction (LVEF), systolic and diastolic blood pressure, and the levels of N-terminal pro-B-type natriuretic peptide, serum potassium, liver enzymes, and renal function markers.

METHODS: This cross-sectional study analyzed data from 64 patients treated for HFrEF with oral spironolactone. Patients were recruited from the Cardiology Outpatient Clinic of the University Hospital, Ostrava, Czech Republic. Blood samples were collected in an outpatient setting from each patient between November 2022 and October 2023 as part of a routine examination to determine steady-state serum canrenone concentrations.

RESULTS: Serum canrenone concentrations ranged from 5.0 to 336.2 µg/L. A correlation was observed between canrenone concentration and both the daily spironolactone dose and dose per kilogram of body weight. However, wide inter-individual variability was observed in canrenone concentrations achieved after administering the same dose of spironolactone and in the concentration-to-dose ratio. Patients with LVEF < 30% used the same dose per day and kilogram of body weight as patients with LVEF ≥ 30% but achieved significantly higher canrenone concentrations. A correlation was observed between canrenone and serum urea, creatinine, and potassium concentrations. An inverse correlation was observed between diastolic blood pressure and dose per kilogram of body weight.

CONCLUSIONS: Wide inter-individual variability in the minimum serum concentrations of canrenone was observed after the same dose of spironolactone was administered. Patients with impaired renal and/or myocardial function were found to be at a higher risk of canrenone accumulation, leading to increased serum potassium concentrations.