Propranolol mitigates sleep apnea-related cardiac responses during CPAP withdrawal: a randomized placebo-controlled cross-over clinical study.

BACKGROUND

Obstructive Sleep Apnea (OSA) causes hemodynamic and autonomic changes during sleep that may promote cardiovascular dysfunction. The extent of heart rate acceleration following respiratory events is associated with mortality in OSA patients. Beta blockers may blunt hemodynamic sequelae of OSA but their impact on heart rate, breathing, sleep and vascular function have not been systematically studied.

METHODS

We performed a double-blind randomized crossover study of long-acting propranolol long-acting (LA, 80 mg) vs. placebo interceded by a 1-week washout in OSA patients. In these patients, we used a 3-night CPAP withdrawal protocol to temporarily elicit severe untreated OSA. Participants received propranolol or placebo at 6:30 PM and underwent polysomnography followed by morning blood pressure (BP), reactive hyperemia index (RHI) and augmentation index (AIX) assessments. The primary outcome was heart rate. Secondary outcomes heart rate trajectory over time, OSA severity, sleep architecture, BP, RHI and AIX. Outcomes were compared non-parametric paired tests, or mixed effects regression for heart rate trajectory.

RESULTS

21 participants (51 ± 11 years old, 62% male, BMI 33.8 ± 6.8 kg/m2) completed the study. Propranolol decreased mean overnight heart rate by 3.6 BPM (p < 0.001). Analysis by event phase revealed that propranolol reduced heart rate during stable sleep and blunted heart rate accelerations associated with apneas, hypopneas and arousals. Propranolol also reduced sleep efficiency, stage N2 sleep percentage and morning diastolic BP was reduced by propranolol but OSA severity, systolic BP, RHI or AIX were unchanged.

CONCLUSION

Propranolol mitigates markers of OSA-related cardiovascular risk including disordered-breathing-related heart rate accelerations but impaired sleep quality. These findings may have therapeutic application for patients with OSA and inform the interpretation of data from patients with OSA taking BB. Clinical Trial Registration. NCT03049306.