Comparative cardiovascular safety of dementia medications: a cross-national study

Emil L Fosbøl; Eric D Peterson; Ellen Holm; Gunnar H Gislason; Yinghong Zhang; Lesley H Curtis; Lars Køber; Isao Iwata; Christian Torp-Pedersen; Soko Setoguchi

doi:10.1111/j.1532-5415.2012.04241.x

Comparative cardiovascular safety of dementia medications: a cross-national study

Emil L Fosbøl, Eric D Peterson, Ellen Holm, Gunnar H Gislason, Yinghong Zhang, Lesley H Curtis, Lars Køber, Isao Iwata, Christian Torp-Pedersen, Soko Setoguchi

Department of Clinical Medicine

13 Citations (Scopus)

Abstract

Objectives To compare the cardiovascular safety of currently marketed dementia medications in new users in the United States and Denmark. Design Retrospective cohort study. Setting Nationally representative sample of Medicare beneficiaries from 2006 through 2009 and nationwide Danish administrative registries from 1997 through 2007. Participants Individuals treated with a dementia medication aged 65 and older. Measurements Hospitalizations for myocardial infarction (MI), heart failure, and syncope or atrioventricular block in both cohorts; fatal or nonfatal MI and cardiac death in the Danish cohort; and all-cause mortality in sensitivity analyses. Results In 46,737 Medicare beneficiaries and 29,496 Danish participants, donepezil was the most frequently used medication. There were no substantial differences in the risk of MI or heart failure between participants using donepezil and those using other cholinesterase inhibitors (all hazard ratios (HR) crossing 1). In the Danish cohort, memantine was associated with fatal or nonfatal MI (HR = 1.33, 95% confidence interval (CI) = 1.08-1.63), cardiac death (HR = 1.31, 95% CI = 1.12-1.53), and a trend toward higher rates of hospitalization for MI (HR = 1.31, 95% CI = 0.98-1.76). Memantine was also associated with greater risk of all-cause mortality in the Medicare (HR = 1.20, 95% CI = 1.13-1.28) and Danish (HR = 1.83, 95% CI = 1.73-1.94) cohorts, suggesting that sicker individuals were selected for memantine therapy. Conclusion Cholinesterase inhibitors have similar cardiovascular risk profiles. Associations between memantine and fatal outcomes in Denmark may be related, in part, to selection of sicker individuals for memantine therapy.

Original language	English
Journal	Journal of the American Geriatrics Society
Volume	60
Issue number	12
Pages (from-to)	2283-9
Number of pages	7
ISSN	0002-8614
DOIs	https://doi.org/10.1111/j.1532-5415.2012.04241.x
Publication status	Published - Dec 2012

Keywords

Aged
Aged, 80 and over
Cholinesterase Inhibitors
Cohort Studies
Dementia
Denmark
Female
Heart Failure
Humans
Indans
Male
Medicare
Memantine
Myocardial Infarction
Nootropic Agents
Piperidines
Receptors, N-Methyl-D-Aspartate
United States

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title = "Comparative cardiovascular safety of dementia medications: a cross-national study",

abstract = "Objectives To compare the cardiovascular safety of currently marketed dementia medications in new users in the United States and Denmark. Design Retrospective cohort study. Setting Nationally representative sample of Medicare beneficiaries from 2006 through 2009 and nationwide Danish administrative registries from 1997 through 2007. Participants Individuals treated with a dementia medication aged 65 and older. Measurements Hospitalizations for myocardial infarction (MI), heart failure, and syncope or atrioventricular block in both cohorts; fatal or nonfatal MI and cardiac death in the Danish cohort; and all-cause mortality in sensitivity analyses. Results In 46,737 Medicare beneficiaries and 29,496 Danish participants, donepezil was the most frequently used medication. There were no substantial differences in the risk of MI or heart failure between participants using donepezil and those using other cholinesterase inhibitors (all hazard ratios (HR) crossing 1). In the Danish cohort, memantine was associated with fatal or nonfatal MI (HR = 1.33, 95% confidence interval (CI) = 1.08-1.63), cardiac death (HR = 1.31, 95% CI = 1.12-1.53), and a trend toward higher rates of hospitalization for MI (HR = 1.31, 95% CI = 0.98-1.76). Memantine was also associated with greater risk of all-cause mortality in the Medicare (HR = 1.20, 95% CI = 1.13-1.28) and Danish (HR = 1.83, 95% CI = 1.73-1.94) cohorts, suggesting that sicker individuals were selected for memantine therapy. Conclusion Cholinesterase inhibitors have similar cardiovascular risk profiles. Associations between memantine and fatal outcomes in Denmark may be related, in part, to selection of sicker individuals for memantine therapy.",

keywords = "Aged, Aged, 80 and over, Cholinesterase Inhibitors, Cohort Studies, Dementia, Denmark, Female, Heart Failure, Humans, Indans, Male, Medicare, Memantine, Myocardial Infarction, Nootropic Agents, Piperidines, Receptors, N-Methyl-D-Aspartate, United States",

author = "Fosb{\o}l, {Emil L} and Peterson, {Eric D} and Ellen Holm and Gislason, {Gunnar H} and Yinghong Zhang and Curtis, {Lesley H} and Lars K{\o}ber and Isao Iwata and Christian Torp-Pedersen and Soko Setoguchi",

note = "{\textcopyright} 2012, Copyright the Authors Journal compilation {\textcopyright} 2012, The American Geriatrics Society.",

year = "2012",

month = dec,

doi = "10.1111/j.1532-5415.2012.04241.x",

language = "English",

volume = "60",

pages = "2283--9",

journal = "Journal of the American Geriatrics Society",

issn = "0002-8614",

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T1 - Comparative cardiovascular safety of dementia medications

T2 - a cross-national study

AU - Fosbøl, Emil L

AU - Peterson, Eric D

AU - Holm, Ellen

AU - Gislason, Gunnar H

AU - Zhang, Yinghong

AU - Curtis, Lesley H

AU - Køber, Lars

AU - Iwata, Isao

AU - Torp-Pedersen, Christian

AU - Setoguchi, Soko

PY - 2012/12

Y1 - 2012/12

N2 - Objectives To compare the cardiovascular safety of currently marketed dementia medications in new users in the United States and Denmark. Design Retrospective cohort study. Setting Nationally representative sample of Medicare beneficiaries from 2006 through 2009 and nationwide Danish administrative registries from 1997 through 2007. Participants Individuals treated with a dementia medication aged 65 and older. Measurements Hospitalizations for myocardial infarction (MI), heart failure, and syncope or atrioventricular block in both cohorts; fatal or nonfatal MI and cardiac death in the Danish cohort; and all-cause mortality in sensitivity analyses. Results In 46,737 Medicare beneficiaries and 29,496 Danish participants, donepezil was the most frequently used medication. There were no substantial differences in the risk of MI or heart failure between participants using donepezil and those using other cholinesterase inhibitors (all hazard ratios (HR) crossing 1). In the Danish cohort, memantine was associated with fatal or nonfatal MI (HR = 1.33, 95% confidence interval (CI) = 1.08-1.63), cardiac death (HR = 1.31, 95% CI = 1.12-1.53), and a trend toward higher rates of hospitalization for MI (HR = 1.31, 95% CI = 0.98-1.76). Memantine was also associated with greater risk of all-cause mortality in the Medicare (HR = 1.20, 95% CI = 1.13-1.28) and Danish (HR = 1.83, 95% CI = 1.73-1.94) cohorts, suggesting that sicker individuals were selected for memantine therapy. Conclusion Cholinesterase inhibitors have similar cardiovascular risk profiles. Associations between memantine and fatal outcomes in Denmark may be related, in part, to selection of sicker individuals for memantine therapy.

AB - Objectives To compare the cardiovascular safety of currently marketed dementia medications in new users in the United States and Denmark. Design Retrospective cohort study. Setting Nationally representative sample of Medicare beneficiaries from 2006 through 2009 and nationwide Danish administrative registries from 1997 through 2007. Participants Individuals treated with a dementia medication aged 65 and older. Measurements Hospitalizations for myocardial infarction (MI), heart failure, and syncope or atrioventricular block in both cohorts; fatal or nonfatal MI and cardiac death in the Danish cohort; and all-cause mortality in sensitivity analyses. Results In 46,737 Medicare beneficiaries and 29,496 Danish participants, donepezil was the most frequently used medication. There were no substantial differences in the risk of MI or heart failure between participants using donepezil and those using other cholinesterase inhibitors (all hazard ratios (HR) crossing 1). In the Danish cohort, memantine was associated with fatal or nonfatal MI (HR = 1.33, 95% confidence interval (CI) = 1.08-1.63), cardiac death (HR = 1.31, 95% CI = 1.12-1.53), and a trend toward higher rates of hospitalization for MI (HR = 1.31, 95% CI = 0.98-1.76). Memantine was also associated with greater risk of all-cause mortality in the Medicare (HR = 1.20, 95% CI = 1.13-1.28) and Danish (HR = 1.83, 95% CI = 1.73-1.94) cohorts, suggesting that sicker individuals were selected for memantine therapy. Conclusion Cholinesterase inhibitors have similar cardiovascular risk profiles. Associations between memantine and fatal outcomes in Denmark may be related, in part, to selection of sicker individuals for memantine therapy.

KW - Aged

KW - Aged, 80 and over

KW - Cholinesterase Inhibitors

KW - Cohort Studies

KW - Dementia

KW - Denmark

KW - Female

KW - Heart Failure

KW - Humans

KW - Indans

KW - Male

KW - Medicare

KW - Memantine

KW - Myocardial Infarction

KW - Nootropic Agents

KW - Piperidines

KW - Receptors, N-Methyl-D-Aspartate

KW - United States

U2 - 10.1111/j.1532-5415.2012.04241.x

DO - 10.1111/j.1532-5415.2012.04241.x

M3 - Journal article

C2 - 23176182

SN - 0002-8614

VL - 60

SP - 2283

EP - 2289

JO - Journal of the American Geriatrics Society

JF - Journal of the American Geriatrics Society

IS - 12

ER -

Comparative cardiovascular safety of dementia medications: a cross-national study

Abstract

Keywords

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