Real-world evidence on the use of benzodiazepine receptor agonists and the risk of venous thromboembolism

Background: Venous thromboembolism (VTE) is a life-threatening disease, and some studies reported that benzodiazepine receptor agonist (BZRA) use could increase the risk of VTE, but this association lacks population-based evidence. Objectives: To investigate the association between BZRA use and the risk of VTE. Patients/Methods: A nested case-control study analyzing Taiwan's claims database was conducted of patients with at least one new BZRA prescription on record from January 1, 2002, to December 31, 2012. We included new users who did not have any BZRA prescriptions in the preceding 2 years and identified cases with VTE and disease risk score matched control subjects. We used a logistic regression model to investigate the association between BZRA exposure and the risk of VTE. The exposure duration, dose, and classes of BZRAs were comprehensively evaluated. Results: We identified 2800 VTE cases and 2800 matched controls. Current BZRA prescription (≤90 days) was associated with VTE occurrence (adjusted odds ratio [aOR]: 1.83; 95% confidence interval [CI], 1.62-2.06). The point estimates of benzodiazepine hypnotics (aOR: 2.00; 95% CI, 1.45-2.76) had a marginally higher risk of VTE than nonbenzodiazepine hypnotics (aOR: 1.39; 95% CI, 1.07-1.81). The VTE risk was increased with combination BZRA use, number of BZRA used, and a higher dose of BZRA. On examination of individual BZRA, the risk of VTE was higher with flunitrazepam use (aOR: 2.99; 95% CI, 1.43-6.28) than other BZRAs. Conclusions: This study presents that current BZRA use may increase the risk of VTE. Also, benzodiazepine hypnotics, especially flunitrazepam, have a higher risk of VTE.