Acetazolamide Improves Outcomes in Decompensated Heart Failure

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In patients with acute decompensated heart failure with volume overload, adding acetazolamide to loop diuretic therapy increases the odds of successful decongestion, concludes a clinical trial report in The New England Journal of Medicine.

The multicenter Acetazolamide in Decompensated Heart Failure with Volume Overload (ADVOR) trial enrolled 519 hospitalized patients with acute decompensated heart failure (63% men; mean age, 78 years). Eligible patients had at least one clinical sign of volume overload (e.g., edema, pleural effusion, or ascites); an N-terminal pro-B-type natriuretic peptide level >1000 pg/mL or B-type natriuretic peptide level >250 pg/mL; and at least 1 month of oral maintenance therapy with furosemide 40 mg or equivalent.

Patients were randomly assigned to acetazolamide, 500 mg intravenously (IV) once daily or placebo added to IV loop diuretics at a dose equivalent to twice the oral maintenance dose. Groups were stratified based on left ventricular ejection fraction with a cutoff of 40%. The main outcome of interest was successful decongestion, defined as no evidence of volume overload within 3 days after randomization with no indications for escalated decongestive therapy.

Acetazolamide was associated with a significant increase in successful decongestion compared with placebo (42.2% vs. 30.5%; risk ratio, 1.46). Patients assigned to acetazolamide had a nonsignificant reduction in a composite secondary outcome of all-cause mortality or heart failure rehospitalization (29.7% and 27.8%, respectively).

The acetazolamide group showed evidence of increased diuretic efficiency with higher cumulative urine output and natriuresis. Rates of worsening kidney function, hypokalemia, hypotension, or adverse events were similar between groups.

Even with high-dose loop diuretics, many patients with acute decompensated heart failure continued signs of volume overload after discharge, associated with poor clinical outcomes. Added to loop diuretics, the carbonic anhydrase inhibitor acetazolamide reduces proximal tubular sodium reabsorption and thus, might improve diuretic efficiency.

The ADVOR results show an increase in successful decongestion with acetazolamide added to standardized loop diuretic therapy for acute decompensated heart failure with volume overload. “These findings highlight the importance of targeting congestion both early and aggressively and support the use of natriuresis as an indicator of diuretic response,” the researchers write [Mullens W, et al. Acetazolamide in acute decompensated heart failure with volume overload. N Engl J Med, published online ahead of print August 27, 2022. doi: 10.1056/NEJMoa2203094;].