Acetazolamide added to loop diuretics improves decongestion in acute heart failure, irrespective of baseline renal function

Reference

Meekers E, Dauw J, Martens P, et al. Renal function and decongestion with acetazolamide in acute decompensated heart failure: the ADVOR trial. Eur Heart J 2023;44(37):3672-3682.

Synopsis

In this prespecified analysis of the the ADVOR trial, investigators evaluated the effect of acetazolamide, as compared with placebo, across the range of patients’ renal function. Of note, patients with an estimated glomerular filtration rate (eGFR) of less than 20 mL/min/1.73 m2 were excluded from the primary ADVOR study population. Patients in each study group received either intravenous acetazolamide 500 mg daily (n = 259) or matching placebo (n = 260) for 3 days, along with standard intravenous loop diuretics. The 2 treatment groups were well-balanced in the proportion of patients with eGFR greater than and less than or equal to 40 mL/min/1.73m2. For the primary outcome of successful decongestion by day 3 of randomization, the acetazolamide group fared better overall (odds ratio 1.97; 95% CI 1.29 - 3.02) after adjustment for baseline differences between patients with high eGFR versus low eGFR. The treatment effect of acetazolamide on the primary endpoint was not modified by high versus low eGFR (P-interaction = .672) or when eGFR was treated as a continuous variable (P-interaction = .977). Acetazolamide led to greater diuresis and natriuresis after 2 days in patients with both low and high eGFR, but there was a higher treatment effect seen in patients with low eGFR (P-interaction = .006). Finally, patients in the acetazolamide arm had a higher incidence of worsening renal function during the treatment phase than did patients in the placebo arm (40.5% vs 18.9%; P < .001), but this difference did not persist at the 3-month follow-up and did not worsen clinical outcomes.