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Full citation: Mullens, W. et al. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload. New Engl J Med 387, 1185–1195 (2022). |
Article type: Therapy (Clinical Trial) |
Rankings: Methods 5/5, Usefulness 3.5/5 |
Introduction
Background
Acute decompensated heart failure is a prevalent condition associated with major morbidity and mortality and results in numerous emergency department visits and hospital admissions.
Objectives
Determine if acetazolamide can improve the efficiency of loop diuretics and enhance decongestion in patients with acute decompensated heart failure.
Methods
Design
The ADVOR trial is a multicenter, parallel-group, double-blind, randomized, placebo-controlled trial. Randomization was stratified by LVEF (≤ 40% or > 40%) and trial site.
Setting
Recruitment between November 2018 and January 2022 at 27 sites across Belgium.
Subjects
Adults admitted for heart failure with signs of fluid overload (edema, pleural effusion or ascites) and elevated NT-proBNP or BNP. Patients were required to be on maintenance oral diuretic therapy and to have had their left ventricular ejection fraction (LVEF) assessed in the previous year.
Intervention
Following randomization, patients received a 500 mg bolus of acetazolamide or placebo once a day in addition to intravenous loop diuretics.
Outcomes
Primary outcome was the proportion of patients with successful decongestion within 3 days after randomization. The congestion score used is a composite of the degree of edema, pleural effusion and ascites.
Results
A total of 2915 patients were evaluated, of whom 519 were randomized to the acetazolamide (259 patients) or placebo (260 patients) group. The primary outcome of decongestion within 3 days occurred in 108/256 patients (42.2%) in the treatment group and in 79/259 (30.5%) in the placebo group (Risk ratio 1.46; 95% CI 1.17–1.82; P < 0.001). Treatment was less effective in patients receiving a higher home maintenance loop diuretic dose.
The secondary outcome of death from any cause or rehospitalization for heart failure during the 3-month follow-up occurred in 76/256 patients (29.7%) in the acetazolamide group and in 72/259 patients (27.8%) in the placebo group (Risk ratio 1.07; 95% CI 0.78–1.48; NS). The duration of hospital stay was 8.8 days (95% CI 8.0–9.5) in the treatment group and 9.9 days (95% CI 9.1–10.8; NS) in the placebo group.
Adverse events frequency was similar in the two groups, and metabolic acidosis did not occur in any patient.
Appraisal
Strengths
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Targets a clinically relevant question
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Robust study design
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Randomization with stratification according to the LVEF
Limitations
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The majority of patients were Caucasian, limiting the generalizability of the results
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The primary outcome (decongestion) is not patient-centered
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The congestion score is infrequently used in clinical practice
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The congestion score depends on subjective clinical examination and is not a validated tool
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Patients with newly diagnosed heart failure were excluded
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Patients treated with SGLT2 inhibitors were excluded
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The power of the study does not allow us to conclude on the absence of adverse effects
Context
Loop diuretics are the mainstay of decongestant therapy and are used as a monotherapy in approximately 70% of patients presenting with acute decompensated heart failure [1, 2]. However, as shown in the Diuretic Optimization Strategies Evaluation (DOSE) trial, few patients achieve complete decongestion after 72 h of loop diuretic treatment [3]. In practice, local internal medicine experts suggest adding hydrochlorothiazide or metolazone for patients resistant to high-dose IV furosemide. Combination therapy with acetazolamide is rarely prescribed for patients admitted with acute decompensated heart failure.
Bottom line
This study adds evidence on diuretic combination strategies to treat decompensated heart failure. The addition of acetazolamide to standard therapy in carefully selected admitted patients increases the odds of having a successful decongestion. Emergency department physicians are unlikely to use combination therapy or acetazolamide in the initial management of acute decompensated heart failure.
References
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Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW. AHA/ACC/HFSA guideline for the management of heart failure: a report of the American college of cardiology/American heart association joint committee on clinical practice guidelines. Circulation. 2022;145:e895–1032. https://doi.org/10.1161/cir.0000000000001063.
Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswal A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF, McNulty SE, Velazquez EJ, Kfoury AG, Chen HH, Givertz MM, Semigran MJ, Bart BA, Mascette AM, Braunwald E, O’Connor CM, Network NHFCR. Diuretic strategies in patients with acute decompensated heart failure. New Engl J Med. 2011;364:797–805. https://doi.org/10.1056/nejmoa1005419.
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Gilbert, S., Desmeules, F., Émond, M. et al. Potential novel therapy in acute decompensated heart failure with volume overload. Can J Emerg Med 25, 587–588 (2023). https://doi.org/10.1007/s43678-023-00527-w
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DOI: https://doi.org/10.1007/s43678-023-00527-w