O028 Combination Pharmacological Therapy Targeting Multiple Mechanisms of Sleep Apnea

Abstract Introduction Currently two leading experimental pharmacological interventions are under investigation for obstructive sleep apnea (OSA). Acetazolamide, which acts to stabilise ventilatory control, lowers the apnea-hypopnea index (AHI) by ∼38%. More recently, atomoxetine-plus-oxybutynin (“AtoOxy”), acting via improvements dilator muscle responsiveness and baseline tone, was found lower AHI >50%. Given that each potential therapy targets a different pathophysiology, we tested whether combined AtoOxy-plus-acetazolamide would be more efficacious than AtoOxy alone. Methods In multicenter randomised crossover trial, 19 patients with moderate-to-severe OSA received (80/5mg respectively), acetazolamide (500mg), AtoOxy-plus-acetazolamide, or placebo at bedtime 3 nights (half-dose on first night); outcomes were assessed night of treatment period. Primary outcome: mixed model analysis compared reduction in AHI(3% desaturation arousal criterion) from between AtoOxy. Secondary included hypoxic burden, index, visual analog scale quality. Results Compared placebo, lowered +49 [33, 62] %baseline (estimate [95%CI]), +47 [31, 61]%baseline, +34 [14, 50]%baseline. However, there no effect vs. alone (−3 [−33, 20]%baseline, P=0.8). outcomes: AtoOxy, burden but differential combination observed. There impact Conclusions While halved AHI, third, these provided greater efficacy