AVDOR: The resurrection of acetazolamide

By Dr. Aswin Babu, edited by Dr. Ahmed El-Medany

At the most recent European Society of Cardiology (ESC) congress, the results of the AVDOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial were presented.

In this multi-centre, double-blinded, randomised controlled trial, a total of 519 patients with acute decompensated heart failure were randomised in a 1:1 fashion to receive either intravenous acetazolamide 500mg (n=259) or placebo (n=260). In addition, patients already on oral loop diuretics were converted to an intravenous dose at double the oral dosage.

Mean age was 78 years with 37.4% of the cohort being female. Some other salient features of the study included a mean LVEF of 43% and a median NT-proBNP of 6,173pg/ml. Successful decongestion, defined as the absence of signs of volume overload, within 3 days after randomization and without an indication for escalation of diuretics was identified as the primary outcome.

A total of 108 (42%) patients met the primary end point in the acetazolamide group compared to 79 (31%) patients in the placebo group (RR 1.46; 95% confidence interval [CI], 1.17 to 1.82; P<0.001). Furthermore, duration of hospital stay was significantly reduced in the acetazolamide arm when compared to loop diuretics (8.8 days vs 9.9 days, p=0.016). Other key secondary outcomes such as all-cause mortality and rehospitalisation for heart failure were comparable between both groups. Reassuringly, during the 3-month follow-up, safety end points such as worsening kidney function, hypokalaemia, hypotension, adverse events were similar between the two arms.

Overall, this study supports the use of acetazolamide as a successful diuretic apparatus in patients with acute decompensated heart failure. Patients were able to achieve quicker and more successful decongestion whilst also reducing the length of inpatient hospital stay. However, limitations exist in the short duration of follow-up as well as the trial excluding patients on SGLT-2 inhibitors. Given the concurrent action of SGLT-2 inhibitors at the level of the proximal renal tubule, the effectiveness of both acetazolamide and SGLT-2 inhibitors in conjunction requires further investigation.

Link to study – https://www.nejm.org/doi/pdf/10.1056/NEJMoa2203094