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


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


Journal Of The American Geriatrics Society, Volume: 60, No.: 12, Pages.: 2283-2289

Year of Publication



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.; © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

Bibtex Citation

@article{Fosb_l_2012, doi = {10.1111/j.1532-5415.2012.04241.x}, url = {}, year = 2012, month = {nov}, publisher = {Wiley-Blackwell}, volume = {60}, number = {12}, pages = {2283--2289}, author = {Emil L. Fosb{o}l and Eric D. Peterson and Ellen Holm and Gunnar H. Gislason and Yinghong Zhang and Lesley H. Curtis and Lars K{o}ber and Isao Iwata and Christian Torp-Pedersen and Soko Setoguchi}, title = {Comparative Cardiovascular Safety of Dementia Medications: A Cross-National Study}, journal = {Journal of the American Geriatrics Society} }


adverse, adverse effects, aged, aged, 80 and over, antagonists inhibitors, chemically induced, cholinesterase, cholinesterase inhibitors, cohort studies, dementia, denmark, donepezil, drug therapy, events, female, heart failure, humans, indans, inhibitors, male, medicare, memantine, myocardial infarction, nootropic agents, piperidines, therapeutic use, united states

Countries of Study

Denmark, USA

Types of Dementia

Dementia (general / unspecified)

Types of Study

Cohort Study

Type of Outcomes


Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions

Anti-Alzheimer medications, e.g.: donezepil, galantamine, rivastigmine, memantime