Effectiveness and safety of acetazolamide plus loop diuretics in acute congestive heart failure: A living systematic review - Version 2026 1.0

Objective: This living systematic review Version 1.0 aims to provide a timely, rigorous and continuously updated summary of the evidence on the use of acetazolamide plus loop diuretics in acute congestive heart failure compared to loop diuretics. Methods: We conducted a comprehensive search in CENTRAL, EMBASE, MEDLINE, and between database inception and September 2025. No language, publication date or status restrictions were applied. Two reviewers independently screened eligible studies, according to predefined selection criteria, and extracted data using a predesigned form. We performed meta-analyses using random-effects models and assessed overall certainty in evidence using the GRADE approach. The quality of the evidence was assessed using the Cochrane risk-of-bias tool. This review was registered in PROSPERO (CRD42024575267). Results: Of 732 records identified, five randomized trials were included, with a total of 1050 participants. The evidence is very uncertain about the effect of adding acetazolamide to loop diuretics in decongestion observed at 72 hours (risk ratio: 1.17, 95% confidence interval: 0.96 to 1.44). Low certainty evidence shows adding acetazolamide to loop diuretics may increase natriuresis at 24 hours (mean difference 38.43, 95% confidence interval: 19.42 to 57.43). No significant differences were found between groups in accumulative diuresis at 48 hours, all-cause mortality, readmission due to heart failure or worsening renal function. Conclusions: Evidence suggests that it is necessary to promote further investigations regarding the use of acetazolamide plus loop diuretics in acute congestive heart failure. More robust, standardized, long-term studies are needed, and conclusions may change as new data emerge.