Acetazolamide to increase natriuresis in congestive heart failure at high risk for diuretic resistance

Introduction Signs and symptoms of congestion are the predominant reason for hospital admission with acute heart failure (AHF). Diuretics are mainstay treatment, but their optimal type and dose regimen remains unclear. Hypothesis Acetazolamide in addition to loop diuretics increases natriuresis without further neurohumoral activation, potentially improving decongestion and outcomes in AHF. Methods This prospective, 2-center study included 34 AHF patients on loop diuretics with volume overload. All patients had a serum sodium concentration 50 and/or admission serum creatinine increased with >0.3 mg/dL compared to baseline. Patients were randomized towards acetazolamide 500 mg OD plus bumetanide 1-2 mg BID versus high-dose loop diuretics (bumetanide BID with bolus dose equal to oral maintenance dose). The primary end-point was natriuresis after 24h. Results Natriuresis after 24h was similar in the combinational treatment versus loop-diuretic only arm (264±126 versus 234±133 mmol, respectively; P-value=0.515). Loop diuretic efficiency, defined as natriuresis corrected for loop diuretic dose, was higher in the group receiving acetazolamide (84±46 versus 52±42 mmol/mg bumetanide, respectively; P-value=0.048; Figure). More patients in the combinational treatment arm had an increase in serum creatinine levels >0.3 mg/dL (P-value=0.046). NT-proBNP reduction and peak neurohumoral activation within 72h were comparable among treatment arms. Median time to all-cause mortality or heart failure readmission was 273 versus 803 days in the group receiving high-dose loop diuretic monotherapy versus acetazolamide with low-dose loop diuretics, which favoured the latter group but was not statistically significant (P-value=0.098). Conclusion Addition of acetazolamide increases the natriuretic response to loop diuretics with similar neurohumoral responses compared to an increase in loop diuretic dose in AHF at high risk for diuretic resistance. ClinicalTrials.gov identifier: NCT01973335.