acetazolamide in acute decompensated heart failure

Last edited 08/2022 and last reviewed 11/2022

Acetazolamide is a carbonic anhydrase inhibitor

  • reduces proximal tubular sodium reabsorption

The ADVOR study:

  • investigated whether acetazolamide, a carbonic anhydrase inhibitor that reduces proximal tubular sodium reabsorption, can improve the efficiency of loop diuretics, in patients with acute decompensated heart failure with volume overload

  • multicenter, parallel-group, double-blind, randomized, placebo-controlled trial

  • assigned patients with acute decompensated heart failure, clinical signs of volume overload (i.e., edema, pleural effusion, or ascites), and an N-terminal pro-B-type natriuretic peptide level of more than 1000 pg per milliliter or a B-type natriuretic peptide level of more than 250 pg per milliliter to receive either intravenous acetazolamide or placebo added to standardized intravenous loop diuretics (at a dose equivalent to twice the oral maintenance dose)

  • randomization was stratified according to the left ventricular ejection fraction (<=40% or >40%)

  • primary end point was successful decongestion, defined as the absence of signs of volume overload, within 3 days after randomization and without an indication for escalation of decongestive therapy

  • secondary end points included a composite of death from any cause or rehospitalization for heart failure during 3 months of follow-up

  • study results:
    • 519 patients included in the trial
      • successful decongestion occurred in 108 of 256 patients (42.2%) in the acetazolamide group and in 79 of 259 (30.5%) in the placebo group (risk ratio, 1.46; 95% confidence interval [CI], 1.17 to 1.82; P<0.001)
      • death from any cause or rehospitalization for heart failure occurred in 76 of 256 patients (29.7%) in the acetazolamide group and in 72 of 259 patients (27.8%) in the placebo group (hazard ratio, 1.07; 95% CI, 0.78 to 1.48), i.e. non-significant statistically
      • acetazolamide treatment was associated with higher cumulative urine output and natriuresis, findings consistent with better diuretic efficiency
      • incidence of worsening kidney function, hypokalemia, hypotension, and adverse events was similar in the two groups
  • conclusion:
    • addition of acetazolamide to loop diuretic therapy in patients with acute decompensated heart failure resulted in a greater incidence of successful decongestion

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