The risk of major adverse cardiovascular events associated with the use of hypnotics in patients with insomnia

Objectives: To examine whether hypnotic use in patients with insomnia reduces major adverse cardiovascular events, including all-cause mortality and nonfatal major adverse cardiovascular events. Methods: Using the Veterans Affairs Corporate Data Warehouse, we conducted a retrospective cohort study of 16,064 patients who were newly diagnosed with insomnia between January 1, 2010, and December 31, 2019. A pair of 3912 hypnotic users and nonusers were selected based on a 1:1 propensity score methodology. The primary outcome was extended major adverse cardiovascular events, a composite of the first occurrence of all-cause mortality or nonfatal major adverse cardiovascular events. Results: During the median follow-up of 4.8 years, a total of 2791 composite events occurred, including 2033 deaths and 762 nonfatal major adverse cardiovascular events. Although the incidence rates of major adverse cardiovascular events were comparable between hypnotic users and nonusers in the propensity-matched cohort, users of benzodiazepines and Z-drugs had a higher risk of all-cause mortality (hazard ratio 1.47 [95% CI, 1.17-1.88] and 1.20 [95% CI, 1.03-1.39], respectively), while serotonin antagonist and reuptake inhibitors users had a survival advantage (hazard ratio 0.79 [95% CI, 0.69-0.91]) compared with nonusers. There were no differences in the risk of nonfatal major adverse cardiovascular events between all classes of hypnotics. Male patients and those aged 60 years or younger who were using benzodiazepines or Z-drugs experienced higher major adverse cardiovascular events than their counterparts. Conclusions: In patients with newly diagnosed insomnia, treatment with hypnotics resulted in higher extended major adverse cardiovascular events but not nonfatal major adverse cardiovascular events with benzodiazepine and Z-drug users compared with nonusers. The use of serotonin antagonist and reuptake inhibitors agents had a protective effect against major adverse cardiovascular events warranting further investigation.