Short-term, Higher Dose Acetazolamide Shown to Improve OSA, CSA

Short-term use of acetazolamide was shown to improve both obstructive sleep apnea (OSA) and central sleep apnea (CSA), with significantly greater reductions in the apnea-hypopnea index (AHI) observed with higher doses, according to study findings published in Chest.

As researchers highlight, OSA and CSA often go untreated due to a lack of available therapies. In some patients with CSA, acetazolamide, a carbonic anhydrase inhibitor, has shown promise in being an effective intervention, although this has not yet been confirmed by clinical trials. Moreover, its efficacy in OSA, which has an overlapping pathophysiology with CSA, remains unknown as well.

Researchers sought to examine the efficacy of acetazolamide in CSA and OSA by conducting a systematic review and meta-analysis of prior studies found on MEDLINE, EMBASE, and ClinicalTrials.gov. The review included studies that reported sleep apnea–related outcomes among adults with OSA/CSA who either received oral acetazolamide or did not (control).

Studies included were published no later than March 11, 2019, and were rated based on their quality of evidence (QOE) via GRADE-methodology. Acetazolamide doses ranged from 36 to 1000 mg/day and treatment duration from 1 to 90 days (median, 6 days). Primary outcomes were AHI and saturation of peripheral oxygen (SpO₂) nadir, which is the patient’s lowest oxygen saturation value.

In the review, 28 studies (13 OSA/15 CSA; acetazolamide subjects: n = 542; control subjects: n = 553) were included, which enabled meta-analyses for 24 outcomes, said the study authors.

When compared with the control group, those administered acetazolamide had lowered AHI by –0.7 effect sizes (95% CI, –0.83 to –0.58; moderate QOE), which corresponded to a reduction of 37.7% (95% CI, –44.7 to –31.3) or 13.8 per hour (95% CI, –16.3 to –11.4; AHI_Control = 36.5/h). Additionally, AHI reduction was found to be similar between OSA and CSA, with significantly greater reductions observed with higher doses at least up to 500 mg per day.

For the other primary outcome, acetazolamide was found to improve SpO₂ nadir by 4.4% (95% CI, 2.3% to 6.5%), but QOE was indicated as very low. Further improvements were observed for several secondary outcomes including sleep quality measures and blood pressure, although these too had very low QOE.

“Rigorous studies with long-term follow-up are warranted to assess acetazolamide's value for the chronic management of sleep apnea patients,” concluded the study authors.

Reference

Schmickl CN, Landry SA, Orr JE, et al. Acetazolamide for obstructive and central sleep apnea: a comprehensive systematic review and meta-analysis. Chest. Published online August 5, 2020. doi:10.1016/j.chest.2020.06.078