Association of alprazolam with major cardiovascular events in patients with hypertension

Rationale: Anxiety is a mediator for emotional reactivity and acute blood pressure elevations, which are associated with an increased risk of cardiovascular death. Alprazolam is a common medication for anxiolysis. We hypothesized that alprazolam usage can reduce the risk of major adverse cardiovascular events (MACEs) in patients with hypertension. Methods: A retrospective cohort study was performed using datasets from Taiwanese Health and Welfare Data. Patients with hypertension were divided into exposed (Alprazolam-exposed) and control groups (non-Alprazolam-exposed) with 1:1 propensity score matching. The study endpoint was the occurrence of MACE. Adjusted hazard ratio (aHR) of MACE risk was estimated using the multiple Cox proportional hazard model. Age-stratified analysis was performed to evaluate the interaction of age and alprazolam use with MACEs. Results: The study cohort consisted of 335 517 alprazolam-exposed patients and 1:1 PSM controls. The mean age was 63.62 ± 12.71 years in the Alprazolam-exposed population. Alprazolam exposure was significantly associated with reduced risk of MACEs (aHR = 0.965, 95% CI = 0.954-0.977), including ischemic stroke (aHR = 0.958, 95% CI = 0.940-0.976), hemorrhagic stroke (aHR = 0.856, 95% CI = 0.821-0.892), myocardial infarction (aHR = 0.933, 95% CI = 0.900-0.968), sudden cardiac death (aHR = 0.955, 95% CI = 0.916-0.996), and all-cause mortality (aHR = 0.921, 95% CI = 0.909-0.932). In the age-subgroup analysis, alprazolam showed the greatest risk reduction effect in hemorrhagic stroke for patients aged <65 years (aHR = 0.779, 95% CI = 0.727-0.835). Conclusion: Alprazolam usage in patients with hypertension was associated with a slightly reduced risk of MACEs and all-cause mortality, and up to 22% reduced risk of hemorrhagic stroke was observed in alprazolam users aged <65 years.