ADVOR
Trial question
What is the role of acetazolamide in patients with acute decompensated HF with volume overload?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
37.0% female
63.0% male
N = 519
519 patients (194 female, 325 male)
Inclusion criteria: patients with acute decompensated HF, clinical signs of volume overload, and NT-proBNP level > 1,000 pg/mL or BNP level > 250 pg/mL
Key exclusion criteria: receipt of acetazolamide maintenance therapy or treatment with another proximal tubular diuretic including a SGLT-2 inhibitor; SBP < 90 mmHg; and an eGFR < 20 mL/min/1.73 m²
Interventions
N=259 acetazolamide (intravenous bolus of 500 mg daily plus standardized intravenous loop diuretics)
N=260 placebo (matching placebo added to standardized intravenous loop diuretics)
Primary outcome
Successful decongestion at 3 days
42.2
30.5
42.2 %
31.7 %
21.1 %
10.6 %
0.0 %
Acetazolamide
Placebo
Significant increase ▲
NNT = 8
Significant increase in successful decongestion at 3 days (42.2% vs. 30.5%; RR 1.46, 95% CI 1.17 to 1.82)
Secondary outcomes
No significant difference in death from any cause or rehospitalization for HF (29.7% vs. 27.8%; HR 1.07, 95% CI 0.78 to 1.48)
Borderline significant decrease in duration of hospital stay (8.8 days vs. 9.9 days; RR 0.89, 95% CI 0.81 to 0.98)
No significant difference in death from any cause or rehospitalization for HF at 3 months (29.7% vs. 27.8%; HR 1.07, 95% CI 0.78 to 1.48)
Safety outcomes
No significant differences in worsening kidney function, hypokalemia, hypotension, and adverse events.
Conclusion
In patients with acute decompensated HF, clinical signs of volume overload, and NT-proBNP level > 1,000 pg/mL or BNP level > 250 pg/mL, acetazolamide was superior to placebo with respect to successful decongestion at 3 days.
Reference
Wilfried Mullens, Jeroen Dauw, Pieter Martens et al. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload. N Engl J Med. 2022 Sep 29;387(13):1185-1195.
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