TY - JOUR
T1 - Association of Selected Antipsychotic Agents With Major Adverse Cardiovascular Events and Noncardiovascular Mortality in Elderly Persons
AU - Sahlberg, Marie
AU - Holm, Ellen
AU - Gislason, Gunnar H
AU - Køber, Lars
AU - Torp-Pedersen, Christian
AU - Andersson, Charlotte
N1 - © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - 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.
AB - 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.
KW - Age Factors
KW - Aged
KW - Aged, 80 and over
KW - Antipsychotic Agents
KW - Cardiovascular Diseases
KW - Cause of Death
KW - Comorbidity
KW - Denmark
KW - Female
KW - Humans
KW - Male
KW - Multivariate Analysis
KW - Odds Ratio
KW - Risk Assessment
KW - Risk Factors
KW - Time Factors
U2 - 10.1161/JAHA.114.001666
DO - 10.1161/JAHA.114.001666
M3 - Journal article
C2 - 26330335
SN - 2047-9980
VL - 4
SP - 1
EP - 12
JO - American Heart Association. Journal. Cardiovascular and Cerebrovascular Disease
JF - American Heart Association. Journal. Cardiovascular and Cerebrovascular Disease
IS - 9
M1 - e001666
ER -
