Long-Term Antipsychotic Use and Major Cardiovascular Events: A Retrospective Cohort Study

Objective: Chronic treatment with antipsychotics may result in both metabolic side effects and cardiovascular disease. Our aim was to evaluate the effect of antipsychotic medications categorized by their metabolic side effect profiles as low, intermediate, or high risk on major cardiovascular events.

Methods: A retrospective cohort study was conducted in adult outpatients aged 30 years or older initiating antipsychotic treatment from 2002 to 2007. Antipsychotic medications were divided into 3 groups (low-, intermediate-, and high-risk) according to the severity of their side-effect profiles in developing metabolic abnormalities associated with cardiovascular disease. The primary outcome measure was the time to the composite of acute myocardial infarction, acute coronary syndrome, ischemic stroke, peripheral artery disease, or a new revascularization procedure. Inverse probability weighting of a marginal structural Cox model was used to adjust for confounding.

Results: A total of 1,008 patients were included (mean age = 72.4 years, median follow-up = 36.5 months), and 19.6% of patients experienced the primary outcome. The adjusted hazard ratios of a major cardiovascular event for patients in the high- or intermediate-risk medication groups compared to the low-risk group were 2.82 (95% CI, 1.57-5.05) and 2.57 (95% CI, 1.43-4.63), respectively.

Conclusions: Older adult patients under antipsychotic regimens with high or intermediate risk of metabolic side effects may face a higher incidence of major cardiovascular events than those under a low-risk regimen during long-term follow-up.