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

Abstract

Aims To investigate the effects of acetazolamide on natriuresis, decongestion, kidney function and neurohumoral activation in acute heart failure (AHF). Methods and results This prospective, two‐centre study included 34 AHF patients on loop diuretics with volume overload. All had a serum sodium concentration < 135 mmol/L and/or serum urea/creatinine ratio > 50 and/or an admission serum creatinine increase of > 0.3 mg/dL compared to baseline. Patients were randomised towards acetazolamide 250–500 mg daily plus bumetanide 1–2 mg bid vs. high‐dose loop diuretics (bumetanide bid with daily dose twice the oral maintenance dose). The primary endpoint was natriuresis after 24 h. Natriuresis after 24 h was similar in the combinational treatment vs. loop diuretic only arm (264 ± 126 vs. 234 ± 133 mmol; P = 0.515). Loop diuretic efficiency, defined as natriuresis corrected for loop diuretic dose, was higher in the group receiving acetazolamide (84 ± 46 vs. 52 ± 42 mmol/mg bumetanide; P = 0.048). More patients in the combinational treatment arm had an increase in serum creatinine levels > 0.3 mg/dL (P = 0.046). N‐terminal pro‐B‐type natriuretic peptide reduction and peak neurohumoral activation within 72 h were comparable among treatment arms. There was a non‐significant trend towards lower all‐cause mortality or heart failure readmissions in the group receiving acetazolamide with low‐dose loop diuretics vs. high‐dose loop diuretic monotherapy (P = 0.098). Conclusion Addition of acetazolamide increases the natriuretic response to loop diuretics compared to an increase in loop diuretic dose in AHF at high risk for diuretic resistance. Trial registration: http://ClinicalTrials.gov NCT01973335.

November 2019 at a glance. Chronic and acute heart failure: from epidemiology to treatment

“…Among 34 patients randomized to acetazolamide plus loop diuretic or high dose of loop diuretic, natriuresis after 24 h (primary endpoint) did not differ in the two groups. However, loop diuretic efficiency as well as renal function impairment were higher in the group receiving acetazolamide …”

The dynamic relationship between serum chloride and cardiorenal syndrome

“…11-60 days) administration of acetazolamide in patients with HF, and reported that it was efficient at maintaining the rise in the serum chloride level and was well tolerated. The Diamox to Increase the Urinary Excretion of Sodium: an Investigational Study in Congestive Heart Failure (DIURESIS-CHF) trial was a randomized controlled study exploring the impact of acetazolamide use on natriuresis, decongestion, and neurohumoral activation in 34 patients with acute HF (mean left ventricular ejection fraction of 43%) and fluid overload who were at high risk for development of diuretic resistance (Verbrugge et al, 2019). In comparison with high dose loop diuretic therapy, addition of acetazolamide to low dose loop diuretics was associated with similar sodium excretion and decongestion, hence increasing loop diuretic efficiency.…”

Down the road from challenges in acute heart failure trials

“…Finally, in the study by Verbrugge et al ., assessment of clinical congestion was performed by the same investigator and increases in diuretic doses in both groups were standardized based on the persistent presence of congestion and poor urine output. Despite this, only 30% of patients were considered euvolaemic after 72 h. These rates are slightly better than the number observed in the DOSE trial (11–18%), however still remain poor .…”

“…In this issue of the Journal, Verbrugge et al 4 have studied the effect of acetazolamide on natriuresis in AHF patients at high risk for diuretic resistance. In this study, 34 AHF patients admitted for decongestive treatment were enrolled.…”

“…9 In the recent position statement on diuretics of the Heart Failure Association of the European Society of Cardiology, assessment of natriuresis in spot urine samples is recommended 2 h after the first administration of loop diuretics, based on which adjustment of diuretic doses should be considered. 6 Finally, in the study by Verbrugge et al, 4 assessment of clinical congestion was performed by the same investigator and increases in diuretic doses in both groups were standardized based on the persistent presence of congestion and poor urine output. Despite this, only 30% of patients were considered euvolaemic after 72 h. These rates are slightly better than the number observed in the DOSE trial (11-18%), however still remain poor.…”