In the ADVOR study of patients with acute decompensated heart failure, the addition of the carbonic anhydrase inhibitor acetazolamide to loop diuretic therapy was associated with a higher incidence of successful decongestion. “Given that residual congestion is linked to adverse outcomes, the beneficial effects of acetazolamide therapy are important,” the authors write. “The higher incidences of decongestion with acetazolamide treatment than with placebo were most probably related to the early and sustained increase in diuresis and natriuresis that were associated with the addition of acetazolamide. These findings highlight the importance of targeting congestion both early and aggressively and support the use of natriuresis as an indicator of diuretic response.”
Participants had acute decompensated heart failure, clinical signs of volume overload such as edema, pleural effusion, or ascites, and elevated levels of N-terminal pro–B-type natriuretic peptide level or a B-type natriuretic peptide. Intravenous acetazolamide 500 mg once daily or placebo added to standardized intravenous loop diuretics (at a dose equivalent to twice the oral maintenance dose) produced these results: “Successful decongestion occurred in 108 of 256 patients (42.2%) in the acetazolamide group and in 79 of 259 (30.5%) in the placebo group (risk ratio, 1.46; 95% confidence interval [CI], 1.17 to 1.82; P <0.001). Death from any cause or rehospitalization for heart failure occurred in 76 of 256 patients (29.7%) in the acetazolamide group and in 72 of 259 patients (27.8%) in the placebo group (hazard ratio, 1.07; 95% CI, 0.78 to 1.48). Acetazolamide treatment was associated with higher cumulative urine output and natriuresis, findings consistent with better diuretic efficiency. The incidence of worsening kidney function, hypokalemia, hypotension, and adverse events was similar in the two groups.”
Editorial: “In contrast to trials of new therapeutic agents, which require regulatory review and approval before they can be used clinically, data from trials of existing drugs such as acetazolamide could potentially be put into practice immediately,” writes an editorialist. “So, where does this leave the clinician approaching the patient who is hospitalized for heart failure with volume overload in 2022? For patients who are likely to have a response to loop diuretics (e.g., those who are younger, those who have less severe or new-onset heart failure, and those who have normal kidney function), treatment with loop diuretics alone is probably sufficient for successful decongestion. However, for the large group of patients who have some degree of diuretic resistance, or for those who have an inadequate initial response to loop-diuretic therapy, these data suggest the use of acetazolamide as a reasonable adjunct to achieving more rapid decongestion. Future studies will further define the role for this strategy in the changing landscape of therapy for patients with heart failure.”