Impact of Reboxetine plus Oxybutynin treatment for Obstructed Sleep Apnea on the Cardiovascular Autonomic Activity

Background: Although we recently reported that a noradrenergic (reboxetine) plus an antimuscarinic (oxybutynin) drugs (reb-oxy) greatly reduced obstructive sleep apnea (OSA) severity, no data are available about the risk of sympathetic overactivity in response to noradrenergic drug intake. We aim to evaluate the impact on the cardiovascular autonomic modulation of 1-week reb-oxy treatment Methods: Participants to a randomized, placebo-controlled, double-blind, crossover trial comparing 4mg reboxetine plus 5mg oxybutynin to placebo for OSA treatment, performed polysomnography (PSG) with ECG for heart rate variability (HRV) evaluation at baseline and after treatments. 24h Ambulatory Blood Pressure Monitoring (ABPM) was also performed baseline and during both treatment periods. Baroreflex sensitivity (BRS) was tested from 10min beat-to-beat blood pressure (BP) recordings in supine and standing positions Results: 16 subjects with (median [IQR]) age 57 [51-61] years and body mass index 30 [26-36] kg/m2 completed the study. Heart rate (HR) from the PSG increased from 65 [60-69] bpm at baseline to 69 [64-77] bpm on reb-oxy and to 66 [59-70] bpm on placebo (p=0.02), while 24h HR measured during the ABPM did not differ between treatment groups. Reb-oxy administration did not modify either the indices of HRV during sleep or daytime and night-time BP levels. Reb-oxy increased BRS without inducing orthostatic hypotension or significant alterations in sympatho/vagal indices Conclusions: The administration of a noradrenergic drug (reboxetine) plus oxybutynin, reducing OSA severity increased the baroreflex sensitivity without inducing clinically relevant sympathetic overactivity