Acetazolamide increases rate of successful decongestion in patients with acute decompensated heart failure

1. In addition to loop diuretic therapy, acetazolamide in patients with acute decompensated heart failure resulted in a greater incidence of successful decongestion.

2. Acetazolamide treatment was associated with higher cumulate urine output and natriuresis.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Currently in patients with acute decompensated heart failure, intravenous (IV) loop diuretics are recommended to ameliorate symptoms of fluid overload. However, despite the use of high-dose loop diuretics, many patients are still discharged from the hospital with residual clinical signs of volume overload. Notably, this is a strong predictor of poor outcomes. Acetazolamide is a carbonic anhydrase inhibitor that reduces proximal tubular sodium reabsorption and may improve diuretic efficiency when added to loop diuretics. However, there is a gap in knowledge as to understanding whether the addition of acetazolamide to standardized IV loop diuretic therapy would improve the incidence of successful decongestion among patients with acute decompensated heart failure. Overall, this study found that the addition of acetazolamide to loop diuretic therapy leads to a higher incidence of successful decongestion in patients with acute decompensated heart failure. This study was limited by limited generalizability to other racial or ethnic groups as nearly all patients in the trial were White. Nevertheless, these study’s findings are significant, as they demonstrate that adding acetazolamide to a standardized loop diuretic therapy in patients with acute decompensated heart failure can significantly improve their odds for successful decongestion and relief of volume overload.

Click to read the study in NEJM

Relevant Reading: New Decongestion Strategies in an Evolving Heart Failure Landscape

In-Depth [randomized controlled trial]: This multicenter, parallel-group, double-blind, randomized placebo-controlled trial assigned patients with acute decompensated heart failure to receive either IV acetazolamide or placebo added to standardized IV loop diuretic therapy. Patients with at least one clinical sign of volume overload (edema, pleural effusion, or ascites) and an N-terminal pro-B-type natriuretic peptide level of more than 100 pg per milliliter or a B-type natriuretic peptide level of more than 250 pg per milliliter were eligible for the study. Patients who received acetazolamide maintenance therapy or treatment with another proximal tubular diuretic including an SGLT inhibitor, a systolic blood pressure of less than 90mmHg, and an estimated glomerular filtration rate of fewer than 20 ml per minute per 1.73 m^2 of the body-surface area were excluded from the study. The primary outcome measured was successful decongestion, defined as the absence of signs of volume overload as assessed by a cardiologist trained in the completion of the congestion score, within three days after randomization without an indication for escalation of decongestive therapy. Outcomes in the primary analysis were assessed via the intention-to-treat principle and a generalized linear mixed model (log-link binomial model). Based on the primary analysis, successful decongestion occurred in 42.2% of the acetazolamide group and in 30.5% of the placebo group (risk ratio 1.46; 95% Confidence Interval [CI] 1.17 to 1.82). Death from any cause or rehospitalization for heart failure occurred in 29.7% of the acetazolamide group and in 27.8% of the placebo group (hazard ratio 1.07; 95% CI 0.78 to 1.48). Acetazolamide treatment was also associated with higher cumulate urine output and natriuresis. Overall, this study demonstrates that when acetazolamide is added to loop diuretic therapy in patients with acute decompensated heart failure, this combination therapy results in a greater incidence of successful decongestion and reduction of volume overload status and symptoms.

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