0980 Benzodiazepine and Z-Drug Use in Adults with Obstructive Sleep Apnea and Cardiometabolic Comorbidities: A Retrospective Cohort Analysis

Abstract Introduction Benzodiazepines and Z-drugs are widely prescribed sedative-hypnotics that alter sleep architecture, blunt arousal responses, and may impair respiratory drive. Their use in patients with obstructive sleep apnea (OSA) is clinically concerning, particularly for individuals with cardiometabolic comorbidities who already face elevated cardiopulmonary risk. Despite widespread prescribing, real-world data on adverse outcomes associated with these medications in OSA populations remain limited. This study evaluated the association between benzodiazepine/Z-drug exposure and subsequent cardiopulmonary outcomes in adults with OSA and coexisting cardiometabolic disease (Smith et al., 2023). Methods We conducted a retrospective cohort study using de-identified electronic health records from 64 U.S. healthcare organizations between July 2005 and July 2025. Adults with documented outpatient encounters and at least one cardiometabolic condition—hypertension, diabetes, or heart failure—were included. Individuals prescribed benzodiazepines or Z-drugs formed the exposure cohort; matched controls had no such prescriptions. Propensity score matching was performed on demographic factors and Charlson Comorbidity Index components. The primary outcomes included incident stroke, heart failure, acute respiratory failure, and all-cause mortality. Relative risks (RRs) and hazard ratios (HRs) were calculated, with age-stratified analyses conducted for robustness. Results The benzodiazepine/Z-drug cohort included 101,296 individuals (mean age 61.7 years), compared with 1,193,812 unexposed individuals (mean age 54.6 years). After matching, each cohort contained 98,219 adults. Benzodiazepine/Z-drug use was associated with higher risk of stroke (RR 0.93; 95% CI 0.89–0.99), heart failure (RR 1.10; 95% CI 1.06–1.14), and acute respiratory failure (RR 1.12; 95% CI 1.06–1.18). Mortality risk was also elevated (HR 1.468; 95% CI 1.42–1.51). Associations remained consistent across age groups. Conclusion In adults with OSA and cardiometabolic comorbidities, benzodiazepine or Z-drug use is associated with increased risk of adverse cardiopulmonary outcomes and mortality. These findings underscore the importance of cautious prescribing, heightened monitoring, and consideration of safer alternatives in this high-risk population. Support (if any)