Benzodiazepine use may carry CV risks among patients with insomnia
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Key takeaways:
- Individuals who regularly used a benzodiazepine to treat insomnia were at a significantly increased risk for CVDs.
- The use of Z-drugs did not increase the risks for CV outcomes among patients with insomnia.
Benzodiazepines were associated with increased risk for CHD, HF and CV mortality among patients with insomnia, according to a study published in the European Journal of Preventive Cardiology.
Previous studies have demonstrated that certain types of hypnotic agents, including nonbenzodiazepines (Z-drugs) and benzodiazepines, may exacerbate the risk for rehospitalization and CV death when used to treat insomnia among patients with HF, according to Yao Xie, MD, MPH, PhD, fellow physician in the department of cardiology at The Second Affiliated Hospital of Zhejiang University School of Medicine in Hangzhou, China, and colleagues. “However, their effects on cardiovascular outcomes in the broader and general population remain insufficiently investigated,” the researchers wrote.
To investigate the association between regular use of Z-drugs (eszopiclone, zolpidem and zaleplon) and benzodiazepines (lorazepam, alprazolam, diazepam and triazolam) and CV outcomes — including CHD, HF, stroke and CV mortality — among patients with insomnia, Xie and colleagues used multivariable Cox proportional hazard models to analyze data from 124,445 UK Biobank participants aged 40 to 69 years with insomnia. Researchers adjusted for cofounders, but because they could not rule out confounding bias, they also performed drug-target Mendelian randomization analyses to address adherent biases and further explore the association between hypnotic agents and CV outcomes.
Overall, 2,544 participants reported regular use of hypnotic agents; specifically, 1,120 solely used Z-drugs, 1,342 solely used benzodiazepines and 82 used both simultaneously.
The researchers reported that regular users of hypnotic agents were more likely to be women, possibly because “females with insomnia are more prone to long-term use of hypnotics along with a relatively higher dose,” they wrote. Regular hypnotic users were also older, more likely to be current smokers and physically inactive, had lower socioeconomic status and education level, and had more comorbidities.
After propensity score matching, 2,541 hypnotic agent users were matched to 5,080 nonusers. Among this cohort, there were 929 CHD cases, 360 HF cases, 262 stroke cases and 180 CV deaths during a median follow-up of 14.3 years.
Although the researchers observed a statistically significant increase in the risk for HF among Z-med users (P = .017), there was no significant association between Z-drugs and CHD, stroke and CV mortality.
They did, however, find a significant association between regular use of benzodiazepines and increased risk for CHD, HF and CV mortality (P < .001).
In subgroup analyses, researchers found women who regularly took Z-drugs were at increased risk for CHD. They noted that this increased risk may be due to pharmacodynamics, such as slower metabolism in women.
The observational and drug-target Mendelian randomization analyses confirmed that Z-drugs did not appear associated with CV risks, according to the researchers. However, the analyses raised safety concerns regarding the CV impact of benzodiazepines, given that the expression of GABRG1, a target of benzodiazepines, was associated with increased risk for HF, stroke and ischemic stroke.
“Overall, consideration should be given to the cardiovascular impact when prescribing benzodiazepines in patients with insomnia,” the researchers wrote.
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