Sodium and potassium changes during decongestion with acetazolamide – A pre‐specified analysis from the ADVOR trial

Abstract

AimsAcetazolamide, an inhibitor of proximal tubular sodium reabsorption, leads to more effective decongestion in acute heart failure (AHF). It is unknown whether acetazolamide alters serum sodium and potassium levels on top of loop diuretics and if baseline values modify the treatment effect of acetazolamide.Methods and resultsThis is a pre‐specified sub‐analysis of the ADVOR trial that randomized 519 patients with AHF and volume overload in a 1:1 ratio to intravenous acetazolamide or matching placebo on top of standardized intravenous loop diuretics. Mean potassium and sodium levels at randomization were 4.2 ± 0.6 and 139 ± 4 mmol/L in the acetazolamide arm versus 4.2 ± 0.6 and 140 ± 4 mmol/L in the placebo arm. Hypokalaemia (<3.5 mmol/L) on admission was present in 44 (9%) patients and hyponatraemia (≤135 mmol/L) in 82 (16%) patients. After 3 days of treatment, 44 (17%) patients in the acetazolamide arm and 35 (14%) patients in the placebo arm developed hyponatraemia (p = 0.255). Patients randomized to acetazolamide demonstrated a slight decrease in mean potassium levels during decongestion, which was non‐significant over time (p = 0.053) and had no significant impact on hypokalaemia incidence (p = 0.061). Severe hypokalaemia (<3.0 mmol/L) occurred in only 7 (1%) patients, similarly distributed between the two treatment arms (p = 0.676). Randomization towards acetazolamide improved decongestive response irrespective of baseline serum sodium and potassium levels.ConclusionsAcetazolamide on top of standardized loop diuretic therapy does not lead to clinically important hypokalaemia or hyponatraemia and improves decongestion over the entire range of baseline serum potassium and sodium levels.

August 2023 at a glance: Focus on epidemiology and medical therapy

“…Acetazolamide was not associated with hyponatraemia. Decongestion was improved irrespective of baseline sodium and potassium levels 25 …”

“…Decongestion was improved irrespective of baseline sodium and potassium levels. 25 A prospective observational study including 50 patients with acute HF, divided into two groups according to the previous use of furosemide (naïve vs. chronic users), showed that the naïve group had a better diuresis and natriuresis compared to the chronic users. Urine furosemide delivery was similar between groups.…”

Advances in Cardiorenal Medicine; the Year 2023 in Review

“…However, there was a signal that the moderate rise in serum creatinine that is seen with acetazolamide use during decongestion may be more pronounced in the setting of HF with reduced ejection fraction. Two additional sub-studies found that the benefits of acetazolamide (natriuresis and diuresis) are consistent across the entire range of renal function, and that this medication does not lead to clinically important hypokalemia or hyponatremia [17,18].…”

Acetazolamide as a decongestion strategy in acute decompensated heart failure: Balancing fluid removal and electrolyte disturbances

“…In this issue of the Journal, Dhont et al 10 . performed a secondary analysis to elucidate if acetazolamide affects serum sodium and potassium levels when used in conjunction with loop diuretics, and if baseline electrolyte values impact the efficacy and/or safety of acetazolamide.…”

“…), rehospitalization, or all-cause mortality at 3 months. In this issue of the Journal, Dhont et al 10 performed a secondary analysis to elucidate if acetazolamide affects serum sodium and potassium levels when used in conjunction with loop diuretics, and if baseline electrolyte values impact the efficacy and/or safety of acetazolamide. Electrolyte abnormalities frequently accompany decongestion therapy, which is observed due to the mechanism of action of loop diuretics.…”