Baseline hypoxic burden (HB)4 may help identify patients with obstructive sleep apnea (OSA), particularly women, whose blood pressure (BP) trajectory is most favorably influenced by AD109 therapy, according to study results presented at the American College of Chest Physicians (CHEST) Annual Meeting, held from October 18 to 21, 2026, in Phoenix, Arizona.

Compared with the apnea-hypopnea index, HB has emerged as a stronger predictor of cardiovascular risk, owing to the increased cardiovascular risk associated with OSA. An investigational neuromuscular modulator, AD109, combining aroxybutynin (2.3 mg) and atomoxetine (75 mg), was shown to improve both apnea severity and HB in phase 3 trials.

In an exploratory study, researchers analyzed morning systolic BP (SBP) and diastolic BP (DBP) at week 26 using pooled safety data (all patients who received ≥1 dose) from the phase 3 SynAIRgy and LunAIRo trials of AD109 in OSA. 

 

…baseline HB4 may help identify OSA patients, particularly women, whose [BP] trajectory is most favorably influenced by AD109.

Using pooled ANCOVA models — which included a treatment-by-log(HB4) interaction term and were adjusted for baseline BP, age, body mass index, and study — treatment effects and moderation by baseline HB4 (defined as the total area under the oxygen desaturation curve across respiratory events meeting the 4% desaturation criterion and normalized by total sleep time [% min/hr]) were evaluated. Additional analyses assessed effect modification by HB4 in sex-specific subgroups.

In the pooled safety set (N=1299; mean [SD] age, 57.2 [10.7] years; 52.5% men), mean baseline morning SBP and DBP were 126.2 and 80.3 mm Hg, respectively, and mean (SD) baseline HB4 was 61.3% (62.6%) minutes per hour (3.8 [0.8] log-transformed).

Each 1-unit increase in log(HB4) at baseline among participants assigned to the placebo group was associated with greater increases in morning SBP (1.37 mm Hg; 95% CI, 0.16-2.59) and DBP (0.86 mm Hg; 95% CI, 0.08-1.64) at week 26. However,  AD109 treatment altered the BP trajectory associated with higher baseline HB4. For each 1-unit increase in log(HB4) among participants receiving AD109, the corresponding changes in morning SBP and DBP were 0.16 mm Hg (95% CI, -1.25 to 1.58; interaction P =.20) and 0.70 mm Hg (95% CI, -0.21 to 1.62; interaction P =.80), respectively, though these values were nonsignificant.

The SBP findings were more pronounced among women (placebo, 2.06 mm Hg per 1-unit log(HB4) vs AD109, -1.54 mm Hg per 1-unit log(HB4); interaction P =.016). DBP was also more pronounced among women (placebo, 1.27 mm Hg vs AD109, 0.36 mm Hg per 1-unit log[HB4]), but the interaction was not significant (interaction P =.322). No evidence of effect modification by baseline HB4 was seen among men for SBP(interaction P =.495) or DBP (interaction P=.444).

The study authors concluded, “These hypothesis-generating findings suggest baseline HB4 may help identify OSA patients, particularly women, whose [BP] trajectory is most favorably influenced by AD109.”