Study Reveals Different CV Risks for Insomnia Medications: Z-Drugs Safe, Benzodiazepines Raise Concerns

A recent study published in the European Journal of Preventive Cardiology has revealed that Z-drugs for insomnia typically do not show a connection to cardiovascular issues, whereas benzodiazepines are associated with cardiovascular risks.

Z-drugs, including medications such as zolpidem, zaleplon, and eszopiclone, are frequently prescribed for short-term management of insomnia. They are generally preferred for their minimal impact on sleep architecture and relatively safer profile. Recent research suggests that these drugs do not carry a substantial risk of cardiovascular harm. In contrast, benzodiazepines, such as diazepam, lorazepam, and alprazolam, have been associated with a higher incidence of cardiovascular issues.

Yao Xie, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China, and colleagues aimed to examine the association between hypnotic agents and cardiovascular outcomes in general individuals with insomnia.

For this purpose, the researchers utilized a propensity score-matched cohort of UK Biobank (UKB) participants with insomnia. They applied the Cox proportional hazards model to estimate the relationship between regular use of hypnotic agents and various cardiovascular outcomes, including coronary heart disease (CHD), heart failure (HF), stroke, and cardiovascular mortality.

To ensure robustness, they conducted sensitivity analyses using inverse probability of treatment weighting, competing risk models and shared frailty models. Additionally, drug-target Mendelian randomization (MR) analyses were employed to further investigate the association between the therapeutic targets of hypnotics and cardiovascular diseases.

The study led to the following findings:

• 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.
• There was no significant association 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 did not alter the above associations.
• Drug-target MR analyses corroborated Z-meds' safety in the general population regarding cardiovascular health.

"Our findings revealed varied associations between different types of hypnotics and the occurrence of cardiovascular events in individuals with insomnia," the researchers wrote.

In the study, benzodiazepines were notably linked to a heightened risk of coronary heart disease, heart failure, and cardiovascular mortality. In contrast, observational and Mendelian randomization analyses found no evidence suggesting that Z-drugs pose a cardiovascular safety risk.

Reference:

Xie, Y., Zhu, S., Wu, S., Liu, C., Shen, J., Jin, C., Ma, H., & Xiang, M. Hypnotic Use and the Risk of Cardiovascular Diseases in Insomnia Patients. European Journal of Preventive Cardiology. https://doi.org/10.1093/eurjpc/zwae263