Abstract
This systematic review and meta-analysis evaluated the efficacy and safety of acetazolamide as an adjunctive diuretic therapy in acute heart failure (AHF) patients. A comprehensive literature search was conducted across multiple electronic databases, including PubMed, Embase, Cochrane Library, and Scopus, identifying seven studies (five randomized controlled trials and two observational studies) that met the eligibility criteria. The analysis revealed that acetazolamide significantly enhanced mean natriuresis (mean differences (MD) 52.72 mmol, 95% confidence interval (CI: 15.52 to 89.92) and mean diuresis (MD 432.88 mmol, 95% CI: 205.82 to 659.93) compared to control groups. However, no significant difference was observed in all-cause mortality between patients receiving acetazolamide and those who did not (relative risks (RR): 1.23, 95% CI: 0.86 to 1.76, p-value: 0.25). While high heterogeneity was reported in natriuresis outcomes (I(2): 90%), diuresis results showed no heterogeneity (I(2): 0%). These findings suggest that acetazolamide effectively enhances fluid removal when used in combination with standard loop diuretics, supporting its role as adjunctive therapy in AHF management. However, limitations, including the small number of studies and inclusion of both RCTs and observational studies, indicate the need for further large-scale trials to better understand acetazolamide's impact on long-term outcomes and identify specific patient populations who may benefit most from this therapy.