Acetazolamide for patients with acute decompensated heart failure with volume overload

Abstract

The Acetazolamide in Decompensated Heart Failure with Volume Overload (ADVOR) trial showed that the addition of acetazolamide to loop diuretic therapy in patients with acute decompensated heart failure (ADHF) in a greater incidence of successful decongestion. 1,2 Description The goal of the trial was to evaluate whether acetazolamide, a carbonic anhydrase inhibitor that reduces proximal tubular sodium reabsorp-tion, can improve the efficiency of loop diuretics, potentially leading to more and faster decongestion in patients with ADHF with volume overload. 3 Study design • Randomization • Parallel • Double-blind • Placebo-controlled • Multicentre (nationwide) • Outcome based on a congestion score (evaluated by a single observer) Patients with ADHF, clinical signs of volume overload (i.e. oedema, pleural effusion, or ascites), and an N-terminal pro-B-type natriuret-ic peptide (NT-proBNP) level of more than 1000 pg per milliliter or a B-type natriuretic peptide (BNP) level of more than 250 pg per milliliter were randomized to receive either intravenous acetazola-mide (500 mg once daily) (n = 259) or placebo (n = 260) added to standardized intravenous loop diuretics (at a dose equivalent to twice the oral maintenance dose). 3 Randomization was stratified according to the left ventricular ejection fraction (≤40% or >40%) and trial site. At randomization, oral loop diuretics were stopped, and the patient received an intravenous loop diuretic at double the oral maintenance dose, administered as a single bolus immediately after randomization and split into two doses (separated by ≥6 h) on each of the next 2 days. The bolus of acetazolamide or matching placebo was administered simultaneously with the first dose of loop diuretics each day. All patients received the same maintenance infusion with 500 mL dextrose 5% and 3 g MgSO4 administered over 24 h until the end of the study treatment phase. Daily oral intake of fluids and sodium was restricted to 1500 mL and 1.5 g, respectively. Patient population • Total number of trial participants: 519 subjects • Duration of follow-up: 3 months • Mean patient age: 78 years • Percentage female: 37% Other salient features/ characteristics • Left ventricular ejection fraction ≤40%: 43% • Median congestion score at baseline [interquartile range (IQR)]: 4 (3-6) • Median NT-proBNP level (IQR): 6173 (3068-10 896) pg per millilitre • Median home maintenance dose of furosemide equivalent (IQR): 60 (40-100) mg Inclusion criteria Patients with an elective or emergency hospital admission and clinical diagnosis of acute heart failure were eligible for the trial if: • ≥1 clinical sign of volume overload (i.e. oedema, ascites confirmed by abdominal ultrasound, or pleural effusion confirmed by a chest X-ray or chest ultrasound). • Maintenance therapy with oral loop diuretics at a dose of ≥1 mg bumetanide or≥40 mg furosemide or≥20 mg torsemide for ≥1 month. • Plasma NT-proBNP level > 1000 pg/mL or BNP level > 250 ng/mL at screening.