Abstract
Background: Chronic insomnia is common in post-menopausal women and is associated with higher cardiovascular disease (CVD) risk. Hypnotics are a second-line therapy after cognitive behavioral therapy for management of chronic insomnia. Among the hypnotics, nonbenzodiazepine GABA agonists (Z-drugs) are commonly prescribed. However, it is unclear whether Z-drug use and other hypnotic use is associated with risk of incident CVD and mortality in older people with sleep disturbances. Objectives: Among post-menopausal women with sleep disturbances, to evaluate the association of Z-drug use compared with use of other prescription hypnotics, and with non-use of any prescription hypnotics with CVD and mortality. Methods: The population studied were post-menopausal women from the Women’s Health Initiative (WHI) Observational Study and Clinical Trials who, at baseline, scored >=9 with the WHI Insomnia Rating Scale (N=40,728). Hypnotic use was ascertained from prescription medications scanned into the Medi-Span database at baseline and first follow-up clinic visit. Frequency of use was ascertained from self-report. Participants were categorized as users of Z-drugs, users of other prescription hypnotics or non-users. Outcomes were composite CVD (congestive heart failure, stroke, and fatal/non-fatal myocardial infarction) and mortality, centrally adjudicated with review of medical records and death certificates. Hazard ratios were estimated from Cox proportional hazards regression models adjusted for demographic, medical history, and sleep measures. To address potential confounding by indication, we also adjusted for propensity to be prescribed hypnotics. Results: At the first follow-up visit 1.1% (424 of 38,979) of participants were users of Z-drugs, 4.2% (1,653 of 38,979) were users of other prescription hypnotics, 3.1% (1,187 of 38,979) had discontinued prescription hypnotic use, and 91.6% (35,715 of 38,979) were non-users at both baseline and first follow-up visit. The mean age of our cohort was 63.6 years (SD = 7.2) and mean follow-up time after the initial follow-up visit was 14.0 years (SD = 6.3). Z-drug use was significantly associated with an increased risk of composite CVD (HR= 1.35, 95%CI: 1.02-1.79) and all-cause mortality (HR= 1.38, 95%CI: 1.13-1.69). Use of other prescription hypnotics and casual use (<=2 times a week) of any hypnotic were not associated with either cardiovascular disease or mortality. Conclusion: Use of Z-drugs three or more times a week was associated with an increased risk of death and cardiovascular disease in post-menopausal women being treated for insomnia. Additional research is needed to evaluate association between frequency of hypnotic use and these outcomes and to investigate possible mechanisms.
Published Version
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