Association of benzodiazepine and Z‐hypnotic use with cardiovascular disease risk: insights from a prospective study of 10 million people in China

Aim To assess the association between Benzodiazepines (BZDs) or Z‐hypnotic use and cardiovascular diseases (CVD) incidence in residents in Beijing, China. Methods We included 2,415,573 individuals with a prescription record for BZDs or Z‐hypnotics in the Beijing Medical Claim Data for Employees database during 2010–2017, and 8,794,356 non‐users with other prescriptions for the same period. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional risk models for 712,850 exposed and 712,850 unexposed participants who were matched 1:1 by propensity score. Results BZDs or Z‐hypnotics users had a higher risk of CVD than non‐users, with an HR of 1.11 (95% CI: 1.10, 1.13). Compared with non‐users, those who used them for less than 3 months had the lowest risk of CVD, and those for more than 5 years had the highest risk, with HRs of 0.50 (0.48, 0.51) and 1.78 (1.72, 1.83), respectively. The risk of CVD was relatively low in those who used only one of the long‐acting BZDs, short‐acting BZDs, or Z‐hypnotics compared to unexposed individuals. Individuals exposed to all three types of drugs had the highest risk, 2.33 (2.22, 2.44) times that of non‐users. Users below the median dose had a lower risk of CVD compared to non‐users, whereas users exceeding the median dose had an increased risk. Conclusion BZD or Z‐hypnotic use in general was nominally associated with an elevated risk of CVD. However, for short‐term, single‐type, and low‐to‐moderate‐dose users, not only did this elevated risk disappear, but drug use also demonstrated a protective effect.