Acetazolamide to increase natriuresis in congestive heart failure at high risk for diuretic resistance

Eur J Heart Fail. 2019 Nov;21(11):1415-1422. doi: 10.1002/ejhf.1478. Epub 2019 May 9.


Aims: To investigate the effects of acetazolamide on natriuresis, decongestion, kidney function and neurohumoral activation in acute heart failure (AHF).

Methods and results: This prospective, two-centre study included 34 AHF patients on loop diuretics with volume overload. All had a serum sodium concentration < 135 mmol/L and/or serum urea/creatinine ratio > 50 and/or an admission serum creatinine increase of > 0.3 mg/dL compared to baseline. Patients were randomised towards acetazolamide 250-500 mg daily plus bumetanide 1-2 mg bid vs. high-dose loop diuretics (bumetanide bid with daily dose twice the oral maintenance dose). The primary endpoint was natriuresis after 24 h. Natriuresis after 24 h was similar in the combinational treatment vs. loop diuretic only arm (264 ± 126 vs. 234 ± 133 mmol; P = 0.515). Loop diuretic efficiency, defined as natriuresis corrected for loop diuretic dose, was higher in the group receiving acetazolamide (84 ± 46 vs. 52 ± 42 mmol/mg bumetanide; P = 0.048). More patients in the combinational treatment arm had an increase in serum creatinine levels > 0.3 mg/dL (P = 0.046). N-terminal pro-B-type natriuretic peptide reduction and peak neurohumoral activation within 72 h were comparable among treatment arms. There was a non-significant trend towards lower all-cause mortality or heart failure readmissions in the group receiving acetazolamide with low-dose loop diuretics vs. high-dose loop diuretic monotherapy (P = 0.098).

Conclusion: Addition of acetazolamide increases the natriuretic response to loop diuretics compared to an increase in loop diuretic dose in AHF at high risk for diuretic resistance.

Trial registration: NCT01973335.

Keywords: Acetazolamide; Cardiorenal syndrome; Diuretics; Natriuresis; Systolic heart failure.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetazolamide / adverse effects
  • Acetazolamide / therapeutic use*
  • Adult
  • Aged
  • Bumetanide / adverse effects
  • Bumetanide / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Resistance*
  • Drug Therapy, Combination
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Humans
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Natriuresis / drug effects*
  • Prospective Studies
  • Risk Factors
  • Sodium Potassium Chloride Symporter Inhibitors / adverse effects
  • Sodium Potassium Chloride Symporter Inhibitors / therapeutic use
  • Survival Analysis


  • Sodium Potassium Chloride Symporter Inhibitors
  • Bumetanide
  • Acetazolamide

Associated data