Acetazolamide in acute decompensated heart failure

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

Reference:

• Mullens W, Dauw J, Martens P, Verbrugge FH, Nijst P, Meekers E, Tartaglia K, Chenot F, Moubayed S, Dierckx R, Blouard P, Troisfontaines P, Derthoo D, Smolders W, Bruckers L, Droogne W, Ter Maaten JM, Damman K, Lassus J, Mebazaa A, Filippatos G, Ruschitzka F, Dupont M; ADVOR Study Group. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload. N Engl J Med. 2022 Aug 27. doi: 10.1056/NEJMoa2203094.