Survival implications of prescription opioid and benzodiazepine use in lung transplant recipients: Analysis of linked transplant registry and pharmacy fill records

Background: Prescription opioid and benzodiazepine use have been associated with morbidity and mortality among some groups of solid organ transplant recipients, but implications for outcomes among lung transplant patients are not well described. Methods: We conducted a retrospective cohort study using linked national transplant registry and pharmaceutical records to characterize the associations between benzodiazepine and opioid prescription fills in the years before and after lung transplant (2006-2017), with risk-adjusted posttransplant survival (adjusted hazard ratio, _LCLaHR_UCL). Results: Among 11,568 recipients, 33.7% filled an opioid prescription, and 25.8% filled a benzodiazepine prescription before transplant. Compared to patients without prescriptions, those who filled both short- and long-acting benzodiazepine prescriptions before transplant had 2-fold higher mortality in the first year posttransplant (aHR, _1.392.12_3.21), after adjustment for baseline factors and opioid fills, while pretransplant opioid fills were not associated with posttransplant mortality after adjustment for benzodiazepine fills. Pretransplant opioid and benzodiazepine use strongly predicted more use after transplant. Fills of both short- and long-acting benzodiazepines in the first year posttransplant were associated with 77% increased mortality >1-to-2 years posttransplant (aHR, _1.061.77_2.96). Compared with no posttransplant opioid fills, there was a dose-dependent association between first-year opioid fills and subsequent adjusted mortality risk (level 2: aHR, _1.171.50_1.92 to level 4: aHR, _1.562.01_2.59). These effects were independent, and interactions were not detected. Conclusions: Benzodiazepine prescription fills before and after lung transplant, and opioid fills after transplant, are independently associated with posttransplant mortality. Review of benzodiazepine and opioid use history is relevant to risk-stratifying patients before and after lung transplant.