Antipsychotics associated with MI in older patients with treated dementia

Antipsychotics are associated with a modestly increased risk for myocardial infarction (MI) in older patients also taking cholinesterase inhibitors for dementia, according to a new study.

Researchers in Quebec used data from a prescription claims database to perform a retrospective cohort study of patients 66 years of age and older who began treatment with cholinesterase inhibitors between Jan. 1, 2000, and Dec. 31, 2009. Patients in the cohort who began using antipsychotics during the study period were matched with a random sample of patients who were not taking antipsychotics. The goal of the study was to determine the association of MI with use of antipsychotics in patients with treated dementia. Results appeared online March 26 at Archives of Internal Medicine.

Among 37,138 patients with treated dementia, 10,969 (29.5%) began taking antipsychotics during the study period. These patients were matched with 10,969 patients who were not taking antipsychotics. Within one year, an MI occurred in 1.3% of those who were taking antipsychotics and 1.2% of those who were not. Compared with patients not taking antipsychotics, the hazard ratios for MI risk were 2.19 (95% CI, 1.11 to 4.32), 1.62 (95% CI, 0.99 to 2.65), 1.36 (95% CI, 0.89 to 2.08), and 1.15 (95% CI, 0.89 to 1.47), respectively, for the first 30 days, first 60 days, first 90 days, and first 365 days. In the case series study, which involved 804 MIs in patients starting antipsychotics, incidence rate ratios for 1 to 30 days, 31 to 60 days, and 61 to 90 days were 1.78 (95% CI, 1.26 to 2.52), 1.67 (95% CI, 1.09 to 2.56), and 1.37 (95% CI, 0.82 to 2.28), respectively.

The authors noted that the start date for antipsychotic therapy may not have been assessed correctly in all patients, among other limitations. However, they concluded that antipsychotics are associated with a modest increase in risk for MI among patients taking cholinesterase inhibitors for dementia, and that this risk is highest in the first month after antipsychotics are started.

An accompanying invited commentary stressed that previous research on this topic is inconsistent and that no biological mechanism can currently explain a relationship between antipsychotics and MI risk.

“Important lessons about the pathogenesis of cardiovascular disease may underlie the observed association between antipsychotic drug use and [acute MI] … but we must await further research to clarify the mechanisms contributing to this association,” the commenting authors wrote. “Meanwhile, physicians should limit prescribing of antipsychotic drugs to patients with dementia and instead use other techniques when available, such as environmental and behavioral strategies, to keep these patients safe and engaged.”