Efficacy of acetazolamide in adult sleep apnea: A systematic review of randomized controlled trials

Background and objectives Sleep-disordered breathing (SDB), encompassing obstructive sleep apnea (OSA) and central sleep apnea (CSA), affects millions of adults worldwide and is associated with significant cardiovascular morbidity. Conventional therapies, particularly continuous positive airway pressure (CPAP), have limitations in certain populations, especially those with CSA or complex sleep apnea. Given the emerging mechanistic rationale for carbonic anhydrase inhibition in stabilizing ventilatory control, this systematic review aimed to evaluate the efficacy of acetazolamide in adult sleep apnea across randomized controlled trials (RCTs).Methods A comprehensive search of PubMed, Scopus, Web of Science, and Cochrane Library identified 462 records. After duplicate removal and screening, 17 RCTs met inclusion criteria. Study quality was assessed using the Cochrane Risk of Bias 2.0 assessment, and data were synthesized narratively due to substantial heterogeneity precluding meta-analysis.Results Acetazolamide generally improved nocturnal oxygenation and reduced respiratory event burden, although effect magnitudes varied across clinical contexts. In low-altitude OSA, reported AHI reductions ranged from approximately 42-69.4%, while in heart failure-associated CSA, CAI decreased by approximately 53%. In healthy adults exposed to altitude, reported improvements included approximately 11 events/h reduction in AHI, 15 events/h reduction in ODI, and 2-5% increases in nocturnal oxygenation. These findings support a context- and phenotype-dependent role for acetazolamide rather than a uniform treatment effect.Conclusions Acetazolamide may be a useful pharmacological adjunct for selected forms of SDB, particularly CSA and altitude-related ventilatory instability, and OSA patients seeking non-CPAP alternatives. Future large-scale, long-term trials are needed to optimize dosing and identify responder endotypes.