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Original ArticleFree Preview

Acetazolamide in Acute Decompensated Heart Failure with Volume Overload

List of authors.
  • Wilfried Mullens, M.D., Ph.D.,
  • Jeroen Dauw, M.D.,
  • Pieter Martens, M.D., Ph.D.,
  • Frederik H. Verbrugge, M.D., Ph.D.,
  • Petra Nijst, M.D., Ph.D.,
  • Evelyne Meekers, M.D.,
  • Katrien Tartaglia, M.Sc.,
  • Fabien Chenot, M.D.,
  • Samer Moubayed, M.D.,
  • Riet Dierckx, M.D., Ph.D.,
  • Philippe Blouard, M.D.,
  • Pierre Troisfontaines, M.D.,
  • David Derthoo, M.D.,
  • Walter Smolders, M.D.,
  • Liesbeth Bruckers, Ph.D.,
  • Walter Droogne, M.D.,
  • Jozine M. Ter Maaten, M.D., Ph.D.,
  • Kevin Damman, M.D., Ph.D.,
  • Johan Lassus, M.D., Ph.D.,
  • Alexandre Mebazaa, M.D., Ph.D.,
  • Gerasimos Filippatos, M.D., Ph.D.,
  • Frank Ruschitzka, M.D.,
  • and Matthias Dupont, M.D.
  • for the ADVOR Study Group*



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.


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.


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.


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 number, NCT03505788.)

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Funding and Disclosures

Supported by the Belgian Health Care Knowledge Center under the KCE Trials Program (KCE-17001).

Disclosure forms provided by the authors are available with the full text of this article at

The views expressed in this article are those of the authors and are not necessarily those of the Belgian Health Care Knowledge Center, which did not influence the analysis or reporting of the trial.

This article was published on August 27, 2022, at

A data sharing statement provided by the authors is available with the full text of this article at

Author Affiliations

From Ziekenhuis Oost-Limburg, Genk (W.M., J.D., P.M., P.N., E.M., K.T., M.D.), Hasselt University, Hasselt (W.M., J.D., E.M., L.B.), Universitair Ziekenhuis Brussel and Vrije Universiteit Brussel, Jette (F.H.V.), Grand Hôpital de Charleroi (F.C.) and Centre Hospitalier Universitaire Charleroi (S.M.), Charleroi, OLV Hospital, Aalst (R.D.), Clinique Saint-Luc, Bouge (P.B.), Centre Hospitalier Régional Citadelle Hospital, Liege (P.T.), AZ Groeninge, Kortrijk (D.D.), AZ Klina, Brasschaat (W.S.), and University Hospitals Leuven, Leuven (W.D.) — all in Belgium; the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (J.M.T.M., K.D.); the Heart and Lung Center, Department of Cardiology, Helsinki University Hospital, and Helsinki University, Helsinki (J.L.); Université Paris Cité, INSERM MASCOT (Cardiovascular Markers in Stressed Conditions), Assistance Publique–Hôpitaux de Paris, Paris (A.M.); the National and Kapodistrian University of Athens and Athens University Hospital Attikon, Athens (G.F.); and Universitäts Spital Zürich, Zurich (F.R.).

Dr. Mullens can be contacted at or at Ziekenhuis Oost-Limburg, Schiepse Bos 6, Genk 3600, Belgium.

A list of the principal investigators in the ADVOR Study Group is provided in the Supplementary Appendix, available at