Whether acetazolamide, a carbonic anhydrase inhibitor that decreases proximal tubular sodium reabsorption, can improve the efficiency of loop diuretics, potentially leading to more and more rapid decongestion in patients with volume overloaded acute decompensated heart failure, is unclear.
In this multicenter, double-blind, randomized, placebo-controlled, parallel-group study, we assigned patients with acute decompensated heart failure, clinical signs of volume overload (i.e., edema, pleural effusion, or ascites), and an N-terminal pro-B type natriuretic peptide level greater than 1000 pg per milliliter or a B-type natriuretic peptide level greater than 250 pg per milliliter to receive either intravenous acetazolamide (500 mg once daily) or placebo added to standardized intravenous loop diuretics (at a dose equivalent to twice the oral maintenance dose). Randomization was stratified by left ventricular ejection fraction (≤40% or >40%). The primary endpoint was successful decongestion, defined as the absence of signs of volume overload, within 3 days of randomization and with no indication of escalation of decongestant therapy. Secondary endpoints included a composite of death from any cause or readmission for heart failure over 3 months of follow-up. Safety was also assessed.
A total of 519 patients were randomized. 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 readmission for heart failure occurred in 76 of 256 patients (29.7%) in the acetazolamide group and 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 renal impairment, hypokalemia, hypotension and adverse events was similar in the two groups.
The addition of acetazolamide to loop diuretic therapy in patients with acute decompensated heart failure resulted in a greater incidence of successful decongestion. (Funded by the Belgian Health Care Knowledge Center; ADVOR ClinicalTrials.gov number, NCT03505788.)