Decongestion with Acetazolamide in Acute Decompensated Heart Failure across the Spectrum of Left Ventricular Ejection Fraction: a Pre-specified Analysis from the ADVOR trial.

<bold>Background: </bold>Acetazolamide inhibits proximal tubular sodium reabsorption and improved decongestion in the Acetazolamide in Decompensated heart failure with Volume OveRload (ADVOR) trial. It remains unclear whether the decongestive effects of acetazolamide differ across the spectrum of left ventricular ejection fraction (LVEF).<bold>Methods: </bold>This is a pre-specified analysis of the randomized, double blind, placebo-controlled ADVOR trial that enrolled 519 patients with acute heart failure, clinical signs of volume overload (edema, pleural effusion or ascites), NTproBNP >1,000 ng/L or BNP >250 ng/ml, to receive intravenous acetazolamide (500 mg once daily) or placebo on top of standardized intravenous loop diuretics (twice oral home maintenance dose). Randomization was stratified according to LVEF (≤40% or >40%). The primary endpoint was successful decongestion, defined as the absence of signs of volume overload within three days from randomization without the need for mandatory escalation of decongestive therapy because of poor urine output.<bold>Results: </bold>Median LVEF was 45% (25-75th percentile: 30-55%) and 43% had a LVEF ≤40%. Patients with lower LVEF were younger, more likely to be male, with a higher prevalence of ischemic heart disease, a higher NTproBNP, less atrial fibrillation, and lower estimated glomerular filtration rate. No interaction on the overall beneficial treatment effect of acetazolamide on the primary endpoint of Successful decongestion (OR=1.77, 95% CI=[1.18-2.63], p=0.005, all p-values for interaction >0.401) was found when LVEF was assessed per randomization stratum (≤/ >40%), or as HFrEF, HFmrEF and HFpEF, or on a continuous scale. Acetazolamide resulted in improved diuretic response measured by higher cumulative diuresis and natriuresis and shortened length of stay without treatment effect modification by baseline LVEF (all p-values for interaction >0.160).<bold>Conclusions: </bold>Acetazolamide when added to treatment with loop diuretics in patients with AHF improves the incidence of successful decongestion, improves diuretic response and shortens length of stay, without treatment effect modification by baseline LVEF. [ABSTRACT FROM AUTHOR]