Clinician Article

Acetazolamide in Acute Decompensated Heart Failure with Volume Overload.

  • Mullens W
  • Dauw J
  • Martens P
  • Verbrugge FH
  • Nijst P
  • Meekers E, et al.
N Engl J Med. 2022 Sep 29;387(13):1185-1195. doi: 10.1056/NEJMoa2203094. Epub 2022 Aug 27. (Original)
PMID: 36027559
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  • Cardiology
    Relevance - 7/7
    Newsworthiness - 7/7
  • Hospital Doctor/Hospitalists
    Relevance - 6/7
    Newsworthiness - 6/7
  • Internal Medicine
    Relevance - 6/7
    Newsworthiness - 6/7
  • Geriatrics
    Relevance - 5/7
    Newsworthiness - 5/7


BACKGROUND: Whether acetazolamide, a carbonic anhydrase inhibitor that reduces proximal tubular sodium reabsorption, can improve the efficiency of loop diuretics, potentially leading to more and faster decongestion in patients with acute decompensated heart failure with volume overload, is unclear.

METHODS: In this multicenter, parallel-group, double-blind, randomized, placebo-controlled trial, we 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 (500 mg once daily) 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%). The 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. Safety was also assessed.

RESULTS: A total of 519 patients underwent randomization. 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). Acetazolamide treatment was associated with higher cumulative urine output and natriuresis, findings consistent with better diuretic efficiency. The incidence of worsening kidney function, hypokalemia, hypotension, and adverse events was similar in the two groups.

CONCLUSIONS: The addition of acetazolamide to loop diuretic therapy in patients with acute decompensated heart failure resulted in a greater incidence of successful decongestion. (Funded by the Belgian Health Care Knowledge Center; ADVOR ClinicalTrials.gov number, NCT03505788.).

Clinical Comments


An "oldie but goodie" that most of us probably never think of in treating acute decompensated CHF. Acetazolamide proved useful in treating these patients.


For cardiologists, this study is practice-changing. Adding acetazolamide to a diuretic regimen reduced the days to achieve euvolemia and symptom improvement. Not associated with any serious side-effects compared with a diuretics-only strategy.


Expected result that using an additional diuretic will cause more diuresis. No clear value for clinical practice since we already know thiazide diuretics have this benefit when added to loop diuretics. In addition, exclusion of SGLT-2 agents further limits the usefulness.


Rates of successful decongestion were aomewhat low in both the intervention and placebo groups.

Hospital Doctor/Hospitalists

When patients did not respond well to iv loop diuretics alone, for a long time we used the combination of loop diuretics and thiazides. Then SGLT2 became available as another option. Now, we have a third option. Unfortunately, there are no studies comparing these options, so we have no way of knowing which is the best one to try first.

Hospital Doctor/Hospitalists

Impressive NNT here. A potentially new addition to the current treatment approach.

Internal Medicine

This will lead to major practice change.

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