Combination diuretic therapy in acute heart failure

This commentary refers to ‘Combining loop with thiazide diuretics for decompensated heart failure: the CLOROTIC trial’, by J. C. Trullàs et al., https://doi.org/10.1093/eurheartj/ehac689 and the discussion piece ‘Combination diuretic therapy in acute heart failure’, by J. C. Trullàs et al., https://doi.org/10.1093/eurheartj/ehad217. Trulls et al. (Nov 2022) concluded that the addition of hydrochlorothiazide (HCTZ) to loop diuretics could improve diuretic response in patients diagnosed with acute heart failure.1 Volume overload management is an important problem in heart failure treatment. Various studies focused on the clinical challenge of loop diuretic resistance. Consistent with previous demonstration, Joan et al. found that patients with acute heart failure may benefit from combination diuretic therapy (CDT). However, there are still some issues needed to be concerned. First, from table 1, we found that the mean left ventricular ejection fraction in the placebo group was 57% and 55% in the HCTZ group. According to the study design and latest guideline,2 the patients in this study were categorized as having heart failure with preserved ejection fraction, which is a little weird in acute heart failure patients. In addition, different other studies including patients with reduced ejection fraction,3,4 further studies may be necessary to apply the conclusion in this study in heart failure with reduced ejection fraction. Second, according to table 1, the estimated glomerular filtration rate (eGFR) is 43.5 mL/min/1.73 m2 in the placebo group and 43.0 mL/min/1.73 m2 in the HCTZ group. This mean that all patients were in stage III of chronic kidney diseases, although the renal function may deteriorate compared with their stable stages. The baseline impaired renal function may explain the findings that HCTZ leaded to increase in creatinine >26.5 μmoL/L or decrease in eGFR >50%. Another study reported that azotemia may develop in patients treated with CDT, particularly in the setting of more advanced baseline renal dysfunction.5 Considering the baseline renal function and high average age (82.0 vs. 83.0), we held the idea that the safe endpoints would improve in younger patients with better renal function. Finally, for the safety endpoints, we found that HCTZ did not reduce the incidence of ‘hard endpoints’ but caused impaired renal function and increased creatinine. There is no data about whether the impaired renal function recovered in the following period. Whether the impaired renal function strike would bring negative effect on the next attack of acute heart failure. All authors offer consent for publication. This work was supported by the National Key Research and Development Program of China (Grant No. 2021ZD0111000). No new data were generated or analyzed in support of this research.