Z-drugs use associated with increased risk of fracture, stroke in dementia

Takeaway

• Higher dose Z-drug use (zaleplon, zopiclone, eszopiclone and zolpidem) in older patients with dementia was associated with an increased risk of falls, fractures and ischaemic stroke.
• These associations were similar or greater in magnitude for higher dose benzodiazepine prescription.

• Higher dose Z-drugs should be avoided, if possible, and non-pharmacological alternatives preferentially considered in dementia.
• Z-drugs prescribed at higher doses should be regularly reviewed in dementia.

• This population-based study evaluated data of 27,090 patients diagnosed with dementia in England between 2000 and 2016 (mean age, 83 years; 62% women). 
• 3532 Z-drug and 5172 benzodiazepine new users were matched to 10,214 and 15,174 non-users, respectively.
• Funding: National Institute of Health Research.

• Compared to non-sedative users with sleep disturbance (n=1833), patients prescribed higher dose Z-drugs (prescriptions equivalent to ≥7.5 mg zopiclone) were at an increased risk of:
  • fractures (adjusted HR [aHR], 1.67; 95% CI, 1.13-2.46);
  • hip fractures (aHR, 1.96; 95% CI, 1.16-3.31);
  • falls (aHR, 1.33; 95% CI, 1.06-1.66); and
  • ischaemic stroke (aHR, 1.88; 95% CI, 1.14-3.10).
• Similar associations were seen when compared with non-sedative users with proximal GP consultation.
• Minimal or inconsistent excess risks were observed with lower doses (≤3.75 mg zopiclone or equivalent daily).
• Z-drug use was associated with greater mortality vs those with sleep disturbance (HR, 1.38; 95% CI, 1.14-1.66), with no strong evidence of excess risk vs non-users (HR, 1.08; 95% CI, 0.94-1.23).
• Z-drug prescription was associated with less mortality than benzodiazepines (HR, 0.73; 95% CI, 0.64-0.83).
• No strong associations were seen between new Z-drug use and greater infection or venous thromboembolism rates, when compared with non-users and benzodiazepine users.

• Risk of residual confounding.