Background: Norepinephrine reuptake inhibitors such as atomoxetine (ato) can improve OSA by increasing pharyngeal muscle activity. Mineralocorticoid antagonists such as spironolactone, may potentiate the reduction of OSA severity. We evaluated if adding spironolactone to atomoxetine (ato-spiro) improved responses in those with OSA and hypertension.

Methods: 21 patients with an apnea-hypopnea index (AHI) between 10-50 events/h and a history of hypertension were recruited and crossed-over to ato 80mg and ato-spiro 80/50mg for 1 week after a 3d low dose run-in in random order. 2 dropped out due to drug-related side effects. Polysomnography and 24-hour BP monitoring were performed at baseline and after each treatment period.

Results:  AHI decreased on both ato and ato-spiro from a baseline mean(SD) of 23.6(10.3) to 10.0(6.7) and 9.9(9.2), respectively (p<0.001 for both). 24-hours systolic BP (mmHg) fell by -5(95%CI: -14,4; p=ns) on ato and -11(-19.5,-2.4; p=0.01) on ato-spiro, diastolic BP dropped by -1.5(-5.8,2.8; p=ns) on ato and -4.1(-8.3,-0.1; p=0.04) on ato-spiro. Both ato and ato-spiro led to significant shift from apnea to hypopnea predominance (p<0.001), and significant reductions in hypoxic burden (p?0.001) and REM sleep (p?0.001).

Conclusions: Both ato-spiro and ato alone decreased OSA severity similarly, but ato-spiro led to greater falls in systolic and diastolic BP. BP reductions were likely due to ato-related improvements in upper airway patency and hypoxemia and spiro-related alterations in cardiorespiratory control. These findings show promise for ato-spiro as an oral treatment for hypertensive OSA patients.