Acetazolamide plus eszopiclone therapy reduces OSA severity in adults

Key takeaways:

• OSA severity improvement was based on placebo-adjusted change in apnea-hypopnea index during supine, non-rapid eye movement sleep.
• Adding venlafaxine resulted in a nonsignificant, “less pronounced” change.

A combination of acetazolamide and eszopiclone taken for 3 days lessened obstructive sleep apnea severity in adults, according to results published in Annals of the American Thoracic Society.

“DualRx (acetazolamide + eszopiclone) was well tolerated and substantially improved OSA,” Christopher N. Schmickl, MD, PhD, of the division of pulmonary, critical care, sleep medicine and physiology at University of California, San Diego, and colleagues wrote. “TripleRx (DualRx + venlafaxine) may have greater effects on OSA-related hypoxemia, but was less well tolerated.”

In the randomized, double-blind, placebo-controlled crossover RESCUE-Combo trial, Schmickl and colleagues evaluated 20 adults (median age, 49 years; 20% women; 60% non-white) with moderate/severe OSA to determine the impact of 3-day acetazolamide plus eszopiclone therapy (DualRx) on apnea-hypopnea index (AHI) during supine, non-rapid eye movement sleep via polysomnography.

A second analysis was performed among those who did not fully respond to DualRx (n = 18) to see if short-term DualRx plus venlafaxine (TripleRx) impacts AHI, according to the study.

At baseline, the median AHI during supine, non-rapid eye movement sleep in the total study population was 32.8 events per hour, suggesting severe OSA.

Researchers reported significant OSA severity improvement with DualRx vs. placebo based on a placebo-adjusted change in AHI during supine, non-rapid eye movement sleep of –13.8 events per hour from baseline.

According to the study, several additional measures significantly improved (P < .05) with DualRx vs. placebo: overall AHI (–11.9 events per hour), hypoxic burden (–11.7 %minute per hour) and sleep architecture.

Notably, analyzing changes in blood pressure, symptoms, heart rate and psychomotor vigilance adjusted for placebo revealed no significant improvement with short-term DualRx, researchers wrote.

During the assessment of TripleRx vs. the two-drug combination, researchers found that this drug combination resulted in a “less pronounced” placebo-adjusted change in AHI during supine, non-rapid eye movement sleep that “did not quite reach statistical significance.”

Switching to TripleRx vs. placebo uncovered a nearly significant improvement in OSA severity (placebo-adjusted change in AHI during supine, non-rapid eye movement sleep, –23.4 events per hour). Additionally, hypoxic burden significantly improved with TripleRx vs. placebo (–30.6 %minute per hour; P = .01), according to the study.

“Addition of venlafaxine led to a more pronounced reduction in AHI [with 4% desaturation], hypoxic burden and possibly AHI_NREM,supine, but attenuated DualRx’s effect on the AHI_NREM,supine, worsened sleep architecture, and increased heart rate, lapses during the PVT, and the number of participants reporting side effects,” Schmickl and colleagues wrote.

In terms of safety, researchers wrote that the two-drug therapy combination “was well tolerated,” and none of the reported adverse events were deemed serious. Common adverse events experienced with DualRx (55%) included paresthesia, polyuria and fatigue, whereas gastrointestinal upset, sleepiness and headache made up the events commonly reported with TripleRx (89%).

“As a next step, we believe longer studies of DualRx in more symptomatic patients sleeping non-supine (and/or using also an oral appliance to minimize the anatomical collapsibility) — and TripleRx with a lower dose of venlafaxine — are warranted to better assess their potential value as future OSA treatments,” Schmickl and colleagues wrote.

“Additionally, more work is needed to help identify responders and clarify mechanisms through which these therapies improve OSA,” Schmickl and colleagues continued.