Background
It is unclear whether acetazolamide, a carbonic anhydrase inhibitor that reduces sodium reabsorption in the proximal tubule, can improve the effectiveness of loop diuretics, which could lead to greater and more rapid decongestion in patients with heart failure. acute decompensated with volume overload.
Methods
In this multicenter, parallel-group, double-blind, randomized, placebo-controlled trial, we assigned patients with acute decompensated heart failure, clinical signs of volume overload (i.e., edema, pleural effusion, or ascites), and an N-terminus. B-type natriuretic peptide level of more than 1000 pg per milliliter or a B-type natriuretic peptide level of more than 250 pg per milliliter to receive intravenous acetazolamide (500 mg once daily) or placebo added to intravenous loop diuretics standardized (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 without an indication for escalation of decongestive therapy. Secondary endpoints included a composite of death from any cause or rehospitalization for heart failure during the 3 months of follow-up. Safety was also evaluated.
Results
A total of 519 patients were randomized. Successful decongestion occurred in 108 of 256 patients (42.2%) in the acetazolamide group and 79 of 259 (30.5%) in the placebo group (relative risk, 1.46; confidence interval [CI]. 95%, 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 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 greater cumulative diuresis and natriuresis, findings consistent with better diuretic efficacy. The incidence of worsening renal function, hypokalemia, hypotension, and adverse events was similar in the two groups.
Conclusions The addition of acetazolamide to loop diuretic therapy in patients with acute decompensated heart failure resulted in a higher incidence of successful decongestion. |
(Funded by the Belgian Healthcare Knowledge Center; ADVOR ClinicalTrials.gov number, NCT03505788. opens in new tab.)
