Acetazolamide, residual congestion and clinical outcomes in acute heart failure - a prespecified analysis of the ADVOR trial

Abstract

Aims: Acetazolamide, an inhibitor of proximal tubular sodium reabsorption, improves decongestion in acute heart failure (AHF). The aim of the current subanalysis is to evaluate which factors influence decongestion success and the impact of acetazolamide on 3-month clinical outcomes. Methods: This analysis of the Acetazolamide in Decompensated heart failure with Volume OveRload (ADVOR) trial, that randomised 519 patients with AHF to intravenous acetazolamide or matching placebo, assessed the relationship between acetazolamide treatment, residual congestion, and all-cause mortality and/or heart failure hospitalisation (HFH). Results: After 90 days, 148 patients (28.7%) experienced the combined endpoint of all-cause mortality and HFH. Predictors of the occurrence of this endpoint were higher baseline doses of loop diuretics (HR = 1.60; 95% CI = [1.26-2.031; p < 0.001) and higher natriuretic peptide levels (HR = 1.34; 95% CI = [1.09-1.651; p = 0.006). Acetazolamide lowered the risk of residual congestion (OR = 0.54, 95% CI = [0.36-0.821), and residual congestion at day 4 (HR = 1.70, 95% CI = [1.18-2.431, p = 0.004) and at discharge (HR = 2.43, 95% CI = [1.76-3.361, p < 0.001) were associated with a worse clinical outcome. The presence of residual congestion despite use of acetazolamide was associated with the highest event rate for all-cause mortality or HFH (p = 0.019). Conclusions: Residual congestion after decongestive treatment for AHF is associated with an increased risk of all-cause mortality and HFH. The upfront addition of acetazolamide reduced the incidence of residual congestion. However, patients with residual congestion despite acetazolamide use are at excessive risk for mortality and HFH, identifying a subset of patients requiring specialised heart failure care.