Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/39777
Title: Decongestion With Acetazolamide in Acute Decompensated Heart Failure Across the Spectrum of Left Ventricular Ejection Fraction: A Prespecified Analysis From the ADVOR Trial
Authors: MARTENS, Pieter 
DAUW, Jeroen 
VERBRUGGE, Frederik 
NIJST, Petra 
MEEKERS, Evelyne 
Augusto, Silvio Nunes, Jr.
Ter Maaten, Jozine M.
Damman, Kevin
Mebazaa, Alexandre
Filippatos, Gerasimos
Ruschitzka, Frank
Tang, W. H. Wilson
DUPONT, Matthias 
MULLENS, Wilfried 
Issue Date: 2023
Publisher: LIPPINCOTT WILLIAMS & WILKINS
Source: CIRCULATION, 147 (3) , p. 201 -211
Abstract: BACKGROUND: Acetazolamide inhibits proximal tubular sodium reabsorption and improved decongestion in the ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial. It remains unclear whether the decongestive effects of acetazolamide differ across the spectrum of left ventricular ejection fraction (LVEF). METHODS: This is a prespecified analysis of the randomized, double-blind, placebo-controlled ADVOR trial that enrolled 519 patients with acute heart failure (HF), clinical signs of volume overload (eg, edema, pleural effusion, or ascites), NTproBNP (N-terminal pro-B-type natriuretic peptide) >1000 ng/L, or BNP (B-type natriuretic peptide) >250 ng/mL to receive intravenous acetazolamide (500 mg once daily) or placebo in addition to standardized intravenous loop diuretics (twice that of the oral home maintenance dose). Randomization was stratified according to LVEF (<= 40% or >40%). The primary end point was successful decongestion, defined as the absence of signs of volume overload within 3 days from randomization without the need for mandatory escalation of decongestive therapy because of poor urine output. RESULTS: Median LVEF was 45% (25th to 75th percentile; 30% to 55%), and 43% had an LVEF <= 40%. Patients with lower LVEF were younger and more likely to be male with a higher prevalence of ischemic heart disease, higher NTproBNP, less atrial fibrillation, and lower estimated glomerular filtration rate. No interaction on the overall beneficial treatment effect of acetazolamide to the primary end point 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 >40%), or as HF with reduced ejection fraction, HF with mildly reduced ejection fraction, and HF with preserved ejection fraction, 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). CONCLUSIONS: When added to treatment with loop diuretics in patients with acute decompensated HF, acetazolamide improves the incidence of successful decongestion and diuretic response, and shortens length of stay without treatment effect modification by baseline LVEF.
Notes: Mullens, W (corresponding author), Hasselt Univ, Schiepse Bos 6, B-3600 Genk, Belgium.
wilfried.mullens@zol.be
Keywords: acetazolamide;heart failured;iuresis;natriuresis
Document URI: http://hdl.handle.net/1942/39777
ISSN: 0009-7322
e-ISSN: 1524-4539
DOI: 10.1161/CIRCULATIONAHA.122.062486
ISI #: 000928052900005
Rights: 2022 American Heart Association, Inc
Category: A1
Type: Journal Contribution
Appears in Collections:Research publications

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