Acetazolamide per os in Decompensated Chronic Heart Failure: Randomized Multicenter Trial ORION-A

Background/Objectives: Overcoming resistance to diuretics is extremely important in decompensated chronic heart failure (HF). The objective of this study was to assess the efficacy and safety of oral acetazolamide, in addition to standard therapy, in HF patients admitted to the hospital with decompensation requiring intravenous loop diuretic therapy. Methods: In this open-label, prospective, multicenter, randomized trial, we included 416 patients hospitalized with decompensated HF. The patients were randomized into two groups: (1) standard therapy, and (2) standard therapy + acetazolamide orally 250 mg 3 times a day in the first 3 days of hospitalization. At randomization, oral thiazide/thiazide-like and loop diuretics were stopped, and intravenous furosemide was initiated. Results: Successful decongestion within 72 h of randomization was observed in 82 patients (39.6%) in the acetazolamide group and in 83 patients (39.7%) in the standard therapy group (p = 0.983). There was a significant difference in the increase in diuresis in the first 72 h (p = 0.028) and in natriuresis on the 2nd day (p = 0.04). There were no differences between the groups in duration of stay in the intensive care unit, duration of index hospitalization, 6 min walk test distance, and clinical assessment scale scores. Death from any cause occurred in three (1.4%) patients in the acetazolamide group, and in the same number of patients in the standard therapy group (p = 0.996). Death from cardiovascular cause and due to decompensated HF also did not differ between the groups during follow-up. Conclusions: The addition of acetazolamide to standard therapy in decompensated chronic HF resulted in a higher cumulative urine output during the first 72 h and natriuresis on the 2nd day after randomization.