Hypoglossal Nerve Stimulation and Hypoxic Burden in Patients With Obstructive Sleep Apnea

Importance: Hypoglossal nerve stimulation has been shown to reduce Apnea-Hypopnea Index (AHI) scores in patients with obstructive sleep apnea (OSA); however, its effect on hypoxic burden (HB), a physiologic marker closely associated with OSA-related risks, remains unclear. Objective: To investigate whether hypoglossal nerve stimulation therapy is associated with reduced HB in patients with OSA, and whether any HB reduction improves daytime sleepiness. Design, Setting, and Participants: This was a secondary analysis of the Stimulation Therapy for Apnea Reduction (STAR) trial, a multicenter, nonrandomized trial with a randomized withdrawal study, conducted from November 10, 2010, to March 23, 2013. Participants were adults with moderate to severe OSA and intolerant of positive airway pressure therapy. Participants with pretreatment and 12-month polysomnography data available were included in this secondary analysis conducted from June to November 2025. Exposures: Hypoglossal nerve stimulation. Main Outcomes and Measures: Twelve-month changes in HB after hypoglossal nerve stimulation therapy-ie, HB reduction and proportion of participants transitioning from high (>63 percentage of minutes per hour [%min/h]) to low HB. A secondary outcome was associated HB reduction and improved Epworth Sleepiness Scale (ESS) scores. Results: The analysis included 108 participants (mean [SD] age, 54.5 [10.3] years; 91 [84.3%] male). Baseline median (IQR) HB was 63.4 (47.8-96.6) %min/h. After 12 months of therapy, the median (IQR) percentage HB reduction was 76.6% (33.1%-90.7%). The posttreatment HB was 21.2 (7.1-53.8) %min/h for the high HB group and 11.3 (6.1-35.9) %min/h for the low HB group. In the high HB group, ESS improvement was associated with HB reductions (β = 1.25; 95% CI, 0.02-2.48), but not with reduced AHI, Arousal Index, or traditional oxygen metrics. In the high HB group (36 responders and 18 nonresponders per Sher-20 criteria), 44 participants (81.5%), including 9 nonresponders, transitioned to low HB after hypoglossal nerve stimulation therapy. In the low HB group, all 36 responders retained their low HB; in addition, 11 of 18 nonresponders (61.1%) showed low HB. Conclusions and Relevance: In this secondary analysis of the STAR trial, hypoglossal nerve stimulation therapy was signficantly associated with reduced HB in patients with OSA. Daytime sleepiness improvement correlated with HB reduction but not with AHI or Arousal Index changes. Notably, at least half of nonresponders showed marked HB improvement, which suggests that HB may serve as a complementary physiologic marker to AHI for assessing treatment response. Trial Registration: ClinicalTrials.gov Identifier: NCT01161420.