Risks of Zolpidem among Patients with Chronic Obstructive Pulmonary Disease.

Castaneda JM, Hee Wai T, Spece LJ, Duan KI, Leonhard A, Griffith MF, Plumley R, Palen BN, Feemster LC, Au DH, Donovan LM. Risks of Zolpidem among Patients with Chronic Obstructive Pulmonary Disease. Annals of the American Thoracic Society. 2023 Nov 2.

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Abstract:

RATIONALE: Non-benzodiazepine benzodiazepine receptor agonists (NBZRA, e.g., zolpidem) are frequently used to treat insomnia among patients with chronic obstructive pulmonary disease (COPD). However, multiple observational studies find that patients with COPD who are prescribed NBZRAs have greater risks for mortality and respiratory complications than patients without such prescriptions. Without an active comparator, these studies are susceptible to confounding by indication. OBJECTIVES: Compare the risk of death or inpatient COPD exacerbation among patients receiving zolpidem relative to patients receiving other hypnotics. METHODS: Using nationwide Veterans Health Administration (VA) data, we identified patients with clinically diagnosed COPD and new receipt of zolpidem or another hypnotic available on VA formulary without prior authorization (melatonin, trazodone, doxepin). We excluded those receiving traditional benzodiazepines or multiple concurrent hypnotics. We propensity-matched patients receiving zolpidem to other hypnotics on 32 variables, including demographics, comorbidities, and markers of COPD severity We compared risk of the primary composite outcome of death or inpatient COPD exacerbation over one year. In secondary analyses, we propensity-matched patients receiving zolpidem to those without hypnotic receipt. RESULTS: Among 283,740 patients meeting inclusion criteria, 1,126 (0.4%) received zolpidem and 3,057 (1.1%) received other hypnotics. We propensity matched patients receiving zolpidem 1:1 to peers receiving other hypnotics. We did not find a difference in the primary composite outcome of death or inpatient exacerbation (HR 0.97, 95%CI 0.0.77-1.23). In secondary analyses comparing patients receiving zolpidem to matched peers without hypnotic receipt, we observed greater risk of death or inpatient exacerbation with zolpidem (HR 1.40, 95%CI 1.09-1.81). CONCLUSIONS: Among patients with COPD, we did not observe greater risks following new receipt of zolpidem relative to other hypnotics. However, we did observe greater risks relative to those without hypnotic receipt. This latter finding may reflect: 1) residual, unmeasured confounding related to insomnia, or, 2) true adverse effects of hypnotics across classes. Future work is needed to better understand the risks of hypnotics in COPD.