Comparison of chlorthalidone and spironolactone as additional diuretic therapy in patients with acute heart failure and preserved ejection fraction

Aims: Patients with acute heart failure (AHF) require intensification in the diuretic strategy. However, the optimal diuretic strategy remains unclear. In this work, we aimed to evaluate the effect of chlorthalidone compared with spironolactone on diuretic efficacy and safety profile in a cohort of patients with AHF and preserved ejection fraction (AHF-pEF).

Methods and results: It was a prospective observational study in a single centre in Spain, included 44 consecutive patients admitted between June 2020 and March 2021, with AHF-pEF in which an additional diuretic was prescribed. The primary endpoint was changes in urinary sodium at 24 and 72 h, and the secondary were urine output, and other security endpoints. Mixed linear regression models were used to analyse the endpoints. Estimates were reported as least squares mean with their respective 95% confidence intervals. The median age of the study population was 85 years (82.5-88.5), and 30 (68.2%) were women. After multivariate analysis, the linear mixed regression analysis confirmed a greater natriuretic response of chlorthalidone over spironolactone, especially at 24 h (P = 0.009). Multivariate analysis also showed a greater cumulative diuretic response in those treated with chlorthalidone (P = 0.001). We did not find significant differences in glomerular filtration rate, serum sodium, and serum potassium at 72 h, neither significant differences were found in 24 and 72 h in systolic blood pressure.

Conclusion: In patients with AHF and left ventricular ejection fraction ≥50% receiving intravenous loop diuretics, chlorthalidone administration was associated with a greater short-term natriuresis.