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Hypnotic use and the risk of cardiovascular diseases in insomnia patients
Yao Xie1, Shiyu Zhu1, Shuang Wu1
1Department of Cardiology, State Key Laboratory of Transvascular Implantation Devices, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang 310009, China.
Insights
Benzodiazepine use in individuals with insomnia is linked to increased cardiovascular risks, including heart disease and death. However, Z-drugs show no significant cardiovascular hazard in this population.
Area of Science:
- Cardiology
- Pharmacology
- Epidemiology
Background:
- Insomnia affects a significant portion of the general population.
- Hypnotic agents are commonly prescribed for insomnia, but their long-term cardiovascular safety is not fully understood.
- Understanding the cardiovascular risks associated with different hypnotic classes is crucial for patient management.
Purpose of the Study:
- To investigate the association between hypnotic agent use and cardiovascular outcomes in individuals with insomnia.
- To differentiate the cardiovascular risks of benzodiazepines versus Z-drugs in an insomnia cohort.
- To provide evidence-based guidance on the cardiovascular safety of hypnotic medications.
Main Methods:
- A propensity score-matched cohort study using UK Biobank (UKB) data.
- Cox proportional hazard models and sensitivity analyses (IPTW, competing risk, shared frailty models) were employed.
- Drug-target Mendelian randomization (MR) analyses assessed the association between therapeutic targets of hypnotics and cardiovascular diseases.
Main Results:
- Over a median follow-up of 14.3 years, no significant association was found between Z-meds and coronary heart disease (CHD), stroke, or cardiovascular mortality.
- Benzodiazepine use was significantly associated with an increased risk of CHD, heart failure (HF), and cardiovascular mortality.
- Sensitivity analyses and drug-target MR analyses corroborated the cardiovascular safety of Z-meds and highlighted concerns with benzodiazepines.
Conclusions:
- Different classes of hypnotics exhibit heterogeneous associations with cardiovascular events in individuals with insomnia.
- Observational and genetic evidence indicates potential cardiovascular safety concerns with benzodiazepine use.
- Z-meds appear to be safe concerning cardiovascular health in the UK Biobank population with insomnia.
Aims:
We aimed to examine the association between hypnotic agents and cardiovascular outcomes in general individuals with insomnia.
Methods And Results:
In a propensity score matched cohort of UK Biobank (UKB) participants with insomnia, Cox proportional hazard model was used to estimate the association between regular use of hypnotic agents and predetermined cardiovascular outcomes including incident coronary heart diseases (CHD), heart failure (HF), stroke, and cardiovascular death. Inverse probability of treatment weighting, competing risk models, and shared frailty models were further performed during sensitivity analysis. Drug-target Mendelian randomization (MR) analyses were employed for further evaluation of the association between therapeutic targets of hypnotics and cardiovascular diseases. During a median follow-up of 14.3 years, the matched cohort documented a total of 929 CHD cases, 360 HF cases, 262 stroke cases, and 180 cardiovascular deaths. No significant association was detected between Z-meds and CHD, stroke, and cardiovascular mortality. Benzodiazepine use was significantly associated with the increased risk of CHD, HF, and cardiovascular mortality. The inverse probability of treatment weighting, competing risk models, and shared frailty models didn't alter the above associations. Moreover, drug-target MR analyses corroborated the safety of Z-meds in the general population regarding cardiovascular health.
Conclusion:
Our findings suggested the heterogeneous associations between different categories of hypnotics and incident cardiovascular events in individuals with insomnia. Both observational and genetic evidence raised safety concerns regarding the cardiovascular impact of benzodiazepines. No cardiovascular hazard of Z-meds was discovered in the UKB population with insomnia.
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