Reviewer: Dr Uğur Ozan DEMİRHAN

Name of the Study: Acetazolamide in Acute Decompensated Heart Failure with Volume Overload (ADVOR)

Published Congress: ESC 2022

Link : https://www.escardio.org/The-ESC/Press-Office/Press-releases/Acetazolamide-improves-decongestion-in-patients-with-acute-decompensated-heart-failure

Background:

Acute heart failure is a life-threatening condition requiring urgent evaluation and treatment. Current guidelines recommend the use of intravenous loop diuretics to ameliorate symptoms of fluid overload in patients with acute decompensated heart failure. Although sequential diuretic therapy has been suggested as a more effective decongestive strategy than loop diuretic therapy alone, decisive evidence regarding effective diuretic agents, administration schedules, and routes of administration is limited. Acetazolamide is a carbonic anhydrase inhibitor that reduces proximal tubular sodium reabsorption and may improve diuretic efficiency when added to loop diuretics, thereby potentially facilitating decongestion.

Objective:

ADVOR investigated whether the addition of acetazolamide to standardized intravenous loop-diuretic therapy would improve the incidence of successful decongestion among patients with acute decompensated heart failure.

Methods:

The trial enrolled 519 adults hospitalised with acute decompensated heart failure who had at least one clinical sign of volume overload (i.e. ascites, pleural effusion, or oedema), elevated natriuretic peptide levels, and had been taking oral diuretics for at least one month at 27 centres in Belgium. Patients were randomly assigned in a 1:1 ratio to receive an intravenous bolus of acetazolamide (500 mg once daily) or matching placebo, administered immediately after randomization and during the next 2 days or until the occurrence of complete decongestion.

The primary end point was successful decongestion, which was defined as the absence of signs of volume overload within three days of randomisation without needing escalation of decongestive therapy. Secondary end points were the composite end point of death from any cause or re-hospitalization for heart failure during 3 months of follow-up and the duration of the index hospital admission.

Results:

Successful decongestion occurred in 108 of 256 patients (42.2%) in the acetazolamide group and in 79 of 259 (30.5%) in the placebo group (risk ratio, 1.46; 95% confidence interval [CI], 1.17 to 1.82; P<0.001) Regarding key secondary endpoints, there was no difference between groups in the composite outcome of all-cause mortality and hospitalisation for heart failure within three months, although patients in the acetazolamide group had a shorter hospital stay compared with those in the placebo group. There did not appear to be a higher incidence of adverse events with acetazolamide treatment (worsening kidney function, hypokalemia and hypotension)

Conclusion:

In this multi-center, randomized, placebo-controlled trial involving patients with acute decompensated heart failure and volume overload, the addition of acetazolamide to standardized intravenous loop-diuretic therapy was associated with a higher incidence of successful decongestion within 3 days after randomization. The addition of acetazolamide to loop-diuretic therapy was not associated with an increased incidence of adverse events, and the higher incidence of successful decongestion was associated with a shorter duration of hospital stay. However, the risk of death from any cause or re-hospitalization for heart failure (secondary composite end point) did not differ significantly between the two trial groups.

Interpretations:

The addition of acetazolamide to standardized intravenous loop-diuretic therapy in patients with acute decompensated heart failure provides to a higher incidence of successful decongestion.