Home > Cardiology > ESC 2022 > Old dogs, new tricks: Acetazolamide plus loop diuretics improves decongestion

Old dogs, new tricks: Acetazolamide plus loop diuretics improves decongestion

Presented By
Prof. Wilfried Mullens, Hospital Oost-Limburg
ESC 2022
Phase 4, ADVOR

Adding acetazolamide, a carbonic anhydrase inhibitor that reduces renal proximal tubular sodium reabsorption, to loop diuretics in patients with acute decompensated heart failure with volume overload improved the rates of successful decongestion within 3 days, according to findings from the ADVOR trial. Because acetazolamide is inexpensive and clinics have >70 years of experience with this off-patent drug, it is anticipated that its wide adoption as a new standard-of-care will improve the speed and efficacy of decongestion, and will save millions of lives.

The audience cheered after the findings from ADVOR (NCT03505788), presented by Prof. Wilfried Mullens (Hospital Oost-Limburg, Belgium), showed that an 8 Euro-per-day drug improved decongestion rates by 12%. The results were simultaneously published in the New England Journal of Medicine [1,2].

Patients with acute decompensated heart failure were randomised to receive standard loop diuretics with addition of either acetazolamide (500 mg intravenously; n=259) or placebo (n=256). At randomisation, oral loop diuretics were stopped and all participants received high-dose intravenous loop diuretics. Participants had an average age of 78 years, the average ejection fraction was 43, and all had at least 1 clinical sign of volume overload (i.e. ascites, pleural effusion, or oedema), elevated natriuretic peptide levels, and had been taking oral diuretics for at least 1 month.

Randomisation was stratified according to the left ventricular ejection fraction (LVEF ≤40% or >40%). The primary endpoint was successful decongestion, defined as no clinical signs of fluid overload within 3 days of randomisation, and without any escalation of decongestive therapy. Secondary endpoints were a composite of death from any cause, rehospitalisation for heart failure during 3 months of follow-up, and safety.

The primary endpoint was met; 42.2% of participants in the acetazolamide group versus 30.5% in the placebo group were successfully decongested within 3 days, with a relative risk (RR) of 1.46 (95% CI 1.17–1.82; P=0.0009). At discharge, 78.8% of the acetazolamide group versus 62.5% of the placebo group had successful decongestion (RR 1.27; 95% CI 1.13–1.43; P=0.0001).

The secondary endpoints revealed other benefits; patients in the acetazolamide arm stayed in hospital for shorter periods (average 8.8 days) compared with those in the placebo arm (average 9.9 days; P=0.02). However, there were no differences between the arms in the composite outcome of all-cause mortality and hospitalisation for heart failure within 3 months (HR 1.07; 95% CI 0.78–1.48). Safety signals were not different between the arms, and the incidence of renal decline, hypokalaemia, hypotension, and adverse events was similar between the 2 groups.

Prof. Mullens concluded: “ADVOR was the largest randomised diuretic trial ever performed in patients with acute decompensated heart failure. Acetazolamide is easy to use, safe, effective, off-patent, and cheap. It is therefore expected that the results of ADVOR will lead to a paradigm shift in the way physicians worldwide treat acute decompensated heart failure.”

  1. Mullens W, et al. ADVOR – Acetazolamide in acute heart failure. Hot Line Session 2, ESC Congress 2022, Barcelona, Spain, 26–29 August.
  2. Mullens W, et al. N Engl J Med. 2022 Aug 27. doi: 10.1056/NEJMoa2203094.


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