Acetazolamide for patients with acute decompensated heart failure: a systematic review and meta-analysis of randomised controlled trials

Abstract Background The role of acetazolamide as an adjunct to standard loop diuretic therapy in patients with acute decompensated heart failure (ADHF) remains uncertain. Purpose We undertook a systematic review and meta-analysis to ascertain the efficacy and safety of acetazolamide plus standard of care (SOC) in patients with ADHF. Methods In January 2024, we systematically searched PubMed, Embase, and Cochrane for randomised controlled trials (RCTs) comparing acetazolamide plus SOC versus SOC alone in patients with ADHF. Effective decongestion was defined as per the definition of each individual study. We pooled risk ratios (RR) and standardized mean difference (SMD) with 95% confidence intervals (CI) for binary and continuous outcomes, respectively. Statistical analyses were performed using Review Manager version 5.4.1. Results We included 4 RCTs comprising 634 patients, of whom 318 (50.1%) were randomised to acetazolamide plus SOC. The mean age was 77.1 years and 64.2% were male. Nearly half of the patients (n=320; 50.5%) had impaired left ventricular ejection fraction at baseline. Most patients had a New York Heart Association functional class III or higher, ranging from 75 to 91% in each study. In the pooled analysis, acetazolamide plus SOC significantly increased the proportion of patients with clinical decongestion at day 3 compared with SOC alone (RR 1.36; 95% CI 1.10 to 1.68; p=0.005; Figure 1A). There was no significant difference between groups in natriuresis at day 1 (SMD 0.46; 95% CI -0.01 to 0.94; p=0.06; Figure 1B) or worsening renal function (RR 1.71; 95% CI 0.73 to 3.98; p=0.22; Figure 1C). Conclusion In this meta-analysis of RCTs among patients admitted with ADHF, acetazolamide plus SOC significantly improved the proportion of patients with clinical decongestion at day 3 relative to SOC alone, without significantly affecting renal function or natriuresis.Figure 1