The ADVOR trial: update on renal interactions

Presented at the ESC Congress 2023 by: Jeroen Dauw, MD - Ghent, Belgium

Introduction and methods

The ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial previously showed that the addition of acetazolamide to loop diuretics in patients with acute decompensated HF is associated with a higher incidence of successful decongestion after 3 days. The aim of this analysis was to evaluate the treatment effect of acetazolamide according to baseline renal function, and to evaluate the effect of acetazolamide on renal function and outcomes.

The ADVOR trial was a multicenter, randomized, double-blind, placebo-controlled trial in which 519 patients with acute decompensated HF who were on loop diuretics IV were randomized to 500 mg acetazolamide once daily or placebo. Main inclusion criteria were: admitted with acute decompensated HF; at least 1 sign of volume overload; at least 1 month of maintenance dose of oral loop diuretics; NT-proBNP >1000 pg/ml or BNP >250 pg/ml. Main exclusion criteria were: acetazolamide maintenance therapy; treatment with SGLT2i; SBP<90 mmHg; eGFR <20 ml/min/1.73m². The primary endpoint was successful decongestion (congestion score ≤1) after 3 days without need for diuretic therapy escalation. Successful decongestion was defined by no pleural effusion, no ascites, and no edema or trace edema.

Main results

• Treatment with acetazolamide was associated with a higher odds of the primary endpoint in the overall study population (OR: 1.97; 95%CI: 1.29-3.02; P=0.002), and in patients with eGFR ≤40 ml/min/1.73m² (OR: 2.32; 95%CI: 1.27-4.24) or eGFR >40 ml/min/1.73m² (OR: 1.79; 95%CI: 0.97-3.30; P for interaction=0.672).
• Acetazolamide increased the odds of complete decongestion at discharge in the overall study population (OR: 2.37; 95%CI: 1.54-3.65; P<0.001), and in patients with eGFR ≤40 ml/min/1.73m² (OR: 1.88; 95%CI: 1.02-3.45) or eGFR >40 ml/min/1.73m² (OR: 3.00; 95%: 1.56-5.77; P for interaction=0.467).
• Acetazolamide did not affect the odds of all-cause mortality and hospitalization for HF in the overall study population, nor in patients with eGFR ≤ or > 40 ml/min/1.73m².
• Acetazolamide increased the odds of successful decongestion across the full range of eGFR.
• At day 2, acetazolamide increased total natriuresis and total urinary output in patients with eGFR ≤40 ml/min/1.73m² and in patients with eGFR >40 ml/min/1.73m², but these effects were more pronounced in patients with eGFR ≤40 ml/min/1.73m².
• During the study treatment period (first 3 days), acetazolamide increased serum creatine levels compared with placebo. However, these differences between treatment groups were not observed after 3 months.
• The incidence of worsening of renal function (defined as ≥0.3 mg/dL increase in creatinine) was higher in the acetazolamide group compared with the placebo group (OR: 2.91; 95%CI: 1.96-4.33).
• There was no difference in the composite of all-cause mortality and hospitalization for HF in patients with worsening renal function or without worsening renal function in both the acetazolamide group and placebo group.
• Successful decongestion reduced the risk of hospitalization for HF in patients with worsening of renal function (HR: 0.51; 95%CI: 0.27-0.94; P=0.032) and without worsening of renal function (HR: 0.63; 95%CI: 0.40-0.99; P=0.046).

Conclusion

Treatment with acetazolamide on top of loop diuretics in patients with acute decompensated HF was associated with a higher incidence of successful decongestion without the need for diuretic therapy escalation across the full (≥20) range of eGFR. Acetazolamide increased natriuresis and total urinary output on day 2 in all patients, these effects were more pronounced in patients with a lower eGFR. Acetazolamide was associated with worsening of renal function. However, there was no difference in serum creatine levels between treatment arms after 3 months. Successful decongestion reduced the risk of HF hospitalization in patients with and without worsening renal function.

- Our reporting is based on the information provided at the ESC Congress 2023 -

The results of this study were simultaneously published in Eur Heart J.