Sodium and Potassium Changes During Decongestion with Acetazolamide – A Pre-Specified Analysis from the ADVOR Trial

AIMS: Acetazolamide, 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 RESULTS: This 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. CONCLUSIONS: Acetazolamide 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.