Clinical question: Does the addition of acetazolamide to standardized loop diuretic therapy achieve more effective decongestion compared to loop diuretics alone in acute decompensated heart failure?
Background: Decompensated heart failure is a leading cause of hospitalization in the U.S. Intravenous (IV) loop diuretics remain the cornerstone of treatment for acute heart failure. Although combination diuretic therapy has been suggested to be more effective than loop diuretics alone, there has previously been a lack of decisive evidence to support this.
Study design: Multicenter, randomized, parallel-group, double-blinded, placebo-controlled study
Setting: 27 sites in Belgium
Synopsis: This study included 519 patients admitted for acute decompensated heart failure who were randomly assigned to receive either acetazolamide 500 mg IV daily (259 patients) or placebo (260 patients) in addition to standardized IV loop diuretics. The primary outcome was complete decongestion at 72 hours, defined as the absence of any clinical sign of fluid overload using a congestion scoring system. Successful decongestion rates were significantly higher in the treatment group (42%) versus the placebo group (31%). Of relevance to hospital medicine, patients treated with acetazolamide had shorter lengths of stay (8.8 days, versus 9.9 days for the placebo arm). There was no statistically significant difference in rates of death or rehospitalization for heart failure within three months. The incidence of worsening kidney function, hypokalemia, hypotension, and adverse events was similar in both groups. Limitations included that 99% of patients identified as white and that patients with newly diagnosed heart failure, severe chronic kidney disease, or concomitant use of SGLT2-inhibitors and other diuretics (except mineralocorticoid receptor antagonists) were excluded.
Bottom line: Acetazolamide is a safe option for combined diuretic therapy, though further investigation is needed in more racially and medically diverse populations.
Citation: Mullens W, et al. Acetazolamide in acute decompensated heart failure with volume overload. N Engl J Med. 2022;387(13):1185-95.
Dr. Chadwick is an internal medicine resident, PGY-2, at Maine Medical Center, Portland, Maine, and Tufts University School of Medicine, Boston.