Heart Failure
Maya A. Harris, PharmD
Recent study findings highlight an alternative approach to combined diuretic treatment in patients with acute heart failure.
Researchers of a prospective, randomized, double-blind, placebo-controlled trial evaluated the safety and efficacy of adding hydrochlorothiazide (HCTZ) to I.V. furosemide in patients with acute heart failure. According to the findings, which were published in the February 2023 issue of European Heart Journal, the addition of HCTZ to loop diuretic therapy improved diuretic response in patients with acute heart failure.
Patients with acute heart failure are traditionally treated with loop diuretics. However, a small subset still struggles with fluid overload. This is due to resistance developed by long-term loop diuretic administration. Some expert clinicians recommend intensifying loop diuretic treatment prior to the addition of HCTZ, but study authors wanted to further explore the synergistic relationship between HCTZ and loop diuretics.
Study methods
The multicenter study included patients 18 years or older who had a history of chronic heart failure and had been hospitalized within the previous 24 hours for acute decompensated heart failure. Other criteria for eligibility included at least 1 month of treatment with oral furosemide 80 mg to 240 mg daily or an equivalent dose of a different loop diuretic.
Exclusion criteria included patients who were unstable upon admission, required renal replacement therapy, or were treated with inotropic agents or with thiazide diuretics 1 month before admission. Patients with low potassium and low sodium levels were also excluded if their values were less than or equal to 2.5 mmol/L and 125 mmol/L, respectively.
At each center, patients were randomized to receive oral HCTZ or placebo for 5 days, with HCTZ doses based on the current function of their kidneys. HCTZ doses were only adjusted to reflect the status of the kidneys. An algorithm based on the DOSE-AHF trial was used to determine the I.V. dose of furosemide. Patients were monitored for the duration of their hospitalization and for an additional 90 days after discharge.
The resulting patient population consisted of 230 patients averaging 83 years old, and 48% were female.
Efficacy outcomes included changes in body weight and patient-reported shortness of breath from baseline to 72 hours of randomization. Safety outcomes included changes in kidney function, low potassium levels, and low sodium levels. Impaired kidney function was defined as an increase in SCr by more than 26.5 µmoL/L or a decrease of more than 50% in serum eGFR. Low potassium levels and low sodium levels met the same criteria as mentioned above.
Results
Patients randomized to the HCTZ group were more likely to lose weight after 72 hours compared to the placebo group. Study authors found that patients treated with HCTZ lost 2.3 kg, while patients treated with the placebo lost 1.5 kg. Regarding patient-reported shortness of breath, there were no significant differences between groups. Similar trends were also observed after 96 hours of randomization, with the HCTZ group losing 2.5 kg and the placebo group losing 1.5 kg.
There was no significant difference in patient-reported shortness of breath between groups.
When it came to kidney function, 46.5% of patients in the HCTZ group met the predetermined safety conditions compared to the 17.2% of patients in the placebo group. No significant changes were observed in potassium levels and sodium levels between the two groups.
Ultimately, the study authors found that the addition of oral HCTZ to I.V. loop diuretics does improve diuretic response, but at the expense of declining kidney function.
Takeaways
This trial is the first of this magnitude to study the safety and efficacy of oral HCTZ in acute heart failure. While the study authors’ findings are consistent with current observational studies, these results emphasize a need to continue robust, prospective experiments to further explore potential adverse events of prolonged treatments in acute heart failure. ■