The ADVOR Trial Evaluated Oral Acetazolamide in Heart Failure
The ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) randomized controlled trial is the definitive study that evaluated oral acetazolamide in heart failure. This trial, referenced in recent clinical guidelines, demonstrated significantly improved decongestion rates compared to placebo when acetazolamide was added to standard loop diuretic therapy 1.
Key Findings of the ADVOR Trial
- Enrolled 519 patients hospitalized with acute decompensated heart failure
- Found successful decongestion in 42.2% of the acetazolamide group versus 30.5% in the placebo group
- Demonstrated greater rates of natriuresis and urine output in the acetazolamide group
- Showed acetazolamide's effectiveness as an adjunctive therapy to loop diuretics 1
Mechanism and Clinical Application
Acetazolamide works by inhibiting carbonic anhydrase in the proximal convoluted tubule, which:
- Reduces sodium reabsorption
- Counters diuretic resistance
- Enhances the effect of loop diuretics 1
The standard dosing for congestive heart failure typically starts at 250-375 mg once daily in the morning, with optimal results when given on alternate days or for two days alternating with a day of rest 2.
Supporting Evidence from Other Studies
Recent meta-analyses and systematic reviews have confirmed the findings of the ADVOR trial:
A 2024 systematic review and meta-analysis of 5 studies (n=684 patients) demonstrated significantly increased natriuresis, urine output, and decongestion in the acetazolamide group compared to controls 3
A pilot study in 2017 showed that adding acetazolamide to the background diuretic regimen in patients with chronic heart failure exacerbations produced additional diuretic effect and alleviated dyspnea 4
Clinical Guidelines Recognition
The European Society of Cardiology guidelines acknowledge the use of acetazolamide:
- In the 2005 guidelines, primarily for correction of alkalosis 5
- In combination therapy for diuretic resistance, though not as first-line therapy 5, 1
Important Considerations
- Acetazolamide is particularly effective when combined with loop diuretics for enhanced decongestion
- It should be used with caution in patients with hypotension, severe hyponatremia, or acidosis
- While acetazolamide improves decongestion markers, it has not demonstrated improvements in hard clinical endpoints like mortality or rehospitalization rates 1
The ADVOR trial represents the most significant advancement in understanding acetazolamide's role in heart failure management, establishing it as a valuable adjunctive therapy for improving decongestion in patients with acute decompensated heart failure.