Table 4.
Mixed Effects Model for Effect of Atomoxetine, Oxybutynin, and Ato-oxy vs Placebo on AHI, Vpassive, Compensation, Arousal Threshold, and Loop Gain During NREM Sleep
| Variable | Vpassive (%eupnea) | Muscle Compensation (%eupnea) | Arousal Threshold (cm H2O) | Loop Gain (Unitless) | AHI (Events/h) |
|---|---|---|---|---|---|
| Model 1 | |||||
| Constant | 63 [43 to 83] P < .001 |
50 [23 to 77] P < .001 |
35 [28 to 42] P < .001 |
0.55 [0.49 to 0.60] P < .001 |
28 [20 to 40] P < .001 |
| Ato-oxy (change from baseline) | 73 [54 to 91] P < .001 |
29 [8 to 51] P = .012 |
–3 [–5 to –1] P = .022 |
–0.06 [–0.12 to –0.01] P = .022 |
–24 [–26 to –21] P < .001 |
| Model 2 | |||||
| Constant | 62 [46 to 78] P < .001 | 43 [21 to 64] P < .001 |
35 [28 to 42] P < .001 |
0.55 [0.50 to 0.61] P < .001 |
30 [21 to 40] P < .001 |
| Atomoxetine (change from baseline) | 38 [21 to 56] P < .001 |
–1 [–22 to +21] P = .96 |
–6 [–11 to –2] P = .003 |
–0.10 [–0.15 to –0.05] P < .001 |
–1 [–10 to 9] P = .64 |
| Oxybutynin (change from baseline) | 18 [4 to 34] P = .019 |
–3 [–21 to +14] P = .70 |
0 [–4 to +4] P = .87 |
0.04 [–0.02 to 0.09] P = .20 |
4 [–5 to 15] P = .30 |
| Interaction (change from baseline) | … | 26 [–7 to 59] P = .15 |
4 [–2 to 10] P = .23 |
… | –24 [–29 to –15] P < .001 |
Results are reported as mean [95% CIs]. Ato-oxy indicates the effect of treatment (combination of atomoxetine and oxybutynin) vs placebo. Due to a skewed distribution, AHI data values were square root transformed for analysis and back-transformed for presentation. Values for Vpassive do not represent observed data (presented in Figures 2 and 3) but rather the underlying collapsibility derived from a sigmoidal transformation function, to handle the ceiling effects previously described for these types of data.6 Values for Muscle Compensation were calculated from Vactive adjusting for Vpassive such that the effect shown is the additional effect on ventilation above Vpassive (thus representing pharyngeal compensation). Constant represents the placebo AHI or trait values. See Table 3 legend for expansion of abbreviations.