Patients with acute decompensated HF were randomized to receive standard loop diuretics with the addition of either acetazolamide (500 mg IV;N=259) or placebo (N=256) for the ADVOR study. At randomization, oral loop diuretics were stopped and all participants received high-dose, IV loop diuretics. Participants had an average age of
78, an average ejection fraction of 43, and at least one clinical sign of volume overload (eg, ascites, pleural effusion, or edema), elevated natriuretic peptide levels, and had been taking oral diuretics for at least 1 month. Randomization was stratified according to the left ventricular ejection fraction (LVEF ≤40% or >40%). The primary endpoint was met; 42.2% of participants in the acetazolamide group versus 30.5% in the placebo group were successfully decongested within 3 days, with a relative risk (RR) of 1.46. At discharge, 78.8% of the acetazolamide group versus 62.5% of the placebo group had successful decongestion (RR, 1.27). Patients in the acetazolamide arm had a shorter hospital length of stay (average, 8.8 days) compared with those in the placebo arm (average, 9.9 days). However, there were no differences between the arms in the composite outcome of all-cause mortality and hospitalization for HF within 3 months (HR, 1.07). Safety signals were not different between the arms, and the incidence rates of renal decline, hypokalemia, hypotension, and adverse events were similar between the groups.