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Keywords:

  • cardiovascular system;
  • cholinesterase inhibitors;
  • dementia;
  • Denmark;
  • drug toxicity;
  • Medicare;
  • memantine;
  • United States

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.