The use of zolpidem to treat insomnia in patients with chronic obstructive pulmonary disease (COPD) is not more likely to result in death or exacerbations than the use of other hypnotics, according to study findings published in the Annals of the American Thoracic Society.

Researchers used data from the Veterans Administration (VA) Corporate Data Warehouse to compare outcomes in patients with COPD who newly received the non-benzodiazepine receptor agonist (NBZRA) zolpidem with outcomes of patients with COPD who newly received other hypnotics for insomnia.

Participants were assigned a VA primary care provider, had at least 2 clinical encounters with COPD within a rolling 12-month period, and had a history of long-term use of inhaled treatment for COPD. Participants had index dates from January 1, 2010, to March 30, 2018, and were followed for a 3-month exposure assessment period and then a 1-year outcome assessment period.

The primary outcome was the combination of all-cause mortality or inpatient COPD exacerbations from 3 to 15 months postindex. The groups were matched using propensity scores that incorporated 32 variables.

[O]ur findings suggest that clinicians concerned about the adverse impact of zolpidem should be similarly concerned about other hypnotics, particularly trazodone.

The analysis included 283,740 participants. During the 3-month exposure assessment period, 1126 patients received zolpidem (mean age, 66.9 [9.9] years; 96% male), 3057 patients received other hypnotics (mean age, 66.1 [10.4] years; 95% male), and 279,557 patients did not receive sedative hypnotics (mean age, 69.7 [10.0] years; 97% male).

The primary analysis matched all 1126 patients in the zolpidem group with 1126 peers in the other hypnotic group. Among the 1126 patients in the other hypnotic group with sufficient overlap in propensity matching scores, 1001 (88.9%) received trazodone, 65 (5.8%) received melatonin, and 60 (5.3%) received doxepin.

At 3 to 15 months postindex, 138 patients in the zolpidem group and 143 matched peers in the other hypnotic group had the primary outcome of inpatient COPD exacerbation or death. No difference was found for the risk for the primary outcome for patients prescribed zolpidem compared with other hypnotics (hazard ratio [HR] for zolpidem, 0.97; 95% CI, 0.77-1.23), and no difference occurred between groups for the secondary outcome of mortality as an independent outcome (HR, 0.92; 95% CI, 0.72-1.19).

A sensitivity analysis propensity-matched patients who received zolpidem only with peers who had trazodone. No difference occurred in death or inpatient COPD exacerbation between the groups (HR, 1.00; 95% CI, 0.79-1.27). An increased risk of death or inpatient COPD exacerbation was observed in the zolpidem group compared with matched peers in the no hypnotic group (HR, 1.40; 95% CI, 1.09-1.81). An increased risk of mortality was an independent outcome (HR, 1.48; 95% CI, 1.12-1.97).

Potential limitations include the lack of access to spirometry or oxygen use in the administrative data. Also, with the exception of trazodone, conclusions are limited regarding the comparable safety of zolpidem with any other specific hypnotic. Additionally, nonpharmacologic therapies were not accounted for in the analysis, and the VA cares for a disproportionately older, male population.

“Overall, our findings demonstrate similar risks associated with the NBZRA zolpidem relative to other hypnotics,” concluded the investigators. “While the risks of hypnotic use in COPD remain unclear, our findings suggest that clinicians concerned about the adverse impact of zolpidem should be similarly concerned about other hypnotics, particularly trazodone.”

Disclosure: One of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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