Association of selected antipsychotic agents with major adverse cardiovascular events and noncardiovascular mortality in elderly persons

Background-data from observational studies have raised concerns about the safety of treatment with antipsychotic agents (aps) in elderly patients with dementia,but this area has been insufficiently investigated. we performed a head-to-head comparison of the risk of major adverse cardiovascular events and noncardiovascular mortality associated with individual aps (ziprasidone,olanzapine,risperidone,quetiapine,levomepromazine,chlorprothixen,flupentixol,and haloperidol) in danish treatment-naïive patients aged =70 years. methods and results-we followed all treatment-näive danish citizens aged >70 years that initiated treatment with aps for the first time between 1997 and 2011 (n=91 774,mean age 82±7 years,35 474 [39%] were men). incidence rate ratios associated with use of different aps were assessed by multivariable time-dependent poisson regression models. for the first 30 days of treatment,compared with risperidone,incidence rate ratios of major adverse cardiovascular events were higher with use of levomepromazine (3.80,95% ci 3.43 to 4.21) and haloperidol (1.85,95% ci 1.67 to 2.05) and lower for treatment with flupentixol (0.54,95% ci 0.45 to 0.66),ziprasidone (0.31,95% ci 0.10 to 0.97),chlorprothixen (0.76,95% ci 0.61 to 0.95),and quetiapine (0.68,95% ci 0.58 to 0.80). relationships were generally similar for long-term treatment. the majority of agents were associated with higher risks among patients with cardiovascular disease compared with patients without cardiovascular disease (p for interaction <0.0001). similar results were observed for noncardiovascular mortality,although differences in associations between patients with and without cardiovascular disease were small. conclusions-our study suggested some diversity in risks associated with individual aps but no systematic difference between first- and second-generation aps. randomized placebo-controlled studies are warranted to confirm our findings and to identify the safest agents. © 2015 the authors.