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-naïve patients aged ≥70 years.


RESULTS
We followed all treatment-naïve 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.
Department of Geriatric Medicine, Aalborg University Hospital, Aalborg, Denmark (M.S.).
Marie
M
Sahlberg
Department of Geriatric Medicine, Nykøbing Falster Hospital, Nykøbing Falster, Denmark (E.H.) Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (E.H., G.H.G., L.).
Ellen
E
Holm
Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (E.H., G.H.G., L.) Department of Cardiology, Gentofte Hospital, Hellerup, Denmark (G.H.G., C.A.) National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark (G.H.G.).
Gunnar H
GH
Gislason
Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (E.H., G.H.G., L.) The Heart Centre, Rigshospitalet, Copenhagen, Denmark (L.).
Lars
L
Køber
Institute of Health, Science and Technology, Aalborg University, Aalborg, Denmark (C.T.P.).
Christian
C
Torp-Pedersen
Department of Cardiology, Gentofte Hospital, Hellerup, Denmark (G.H.G., C.A.).
Charlotte
C
Andersson
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D002423:Cause of Death; D015897:Comorbidity; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
D014150:Antipsychotic Agents
antipsychotic medications; cardiovascular risks; elderly