title: The use of cholinesterase inhibitors and the risk of myocardial infarction and death: a nationwide cohort study in subjects with Alzheimer's disease.
abstract: OBJECTIVE
  Cholinesterase inhibitors (ChEIs) are used for symptomatic treatment of Alzheimer's disease. These drugs have vagotonic and anti-inflammatory properties that could be of interest also with respect to cardiovascular disease. This study evaluated the use of ChEIs and the later risk of myocardial infarction and death.
  
  
  RESULTS
  The cohort consisted of 7073 subjects (mean age 79 years) from the Swedish Dementia Registry with the diagnoses of Alzheimer's dementia or Alzheimer's mixed dementia since 2007. Cholinesterase inhibitor use was linked to diagnosed myocardial infarctions (MIs) and death using national registers. During a mean follow-up period of 503 (range 0-2009) days, 831 subjects in the cohort suffered MI or died. After adjustment for confounders, subjects who used ChEIs had a 34% lower risk for this composite endpoint during the follow-up than those who did not [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.56-0.78]. Cholinesterase inhibitor use was also associated with a lower risk of death (HR: 0.64, 95% CI: 0.54-0.76) and MI (HR: 0.62, 95% CI: 0.40-0.95) when analysed separately. Subjects taking the highest recommended ChEI doses (donepezil 10 mg, rivastigmine >6 mg, galantamine 24 mg) had the lowest risk of MI (HR: 0.35, 95% CI: 0.19-0.64), or death (HR: 0.54, 95% CI: 0.43-0.67) compared with those who had never used ChEIs.
  
  
  CONCLUSIONS
  Cholinesterase inhibitor use was associated with a reduced risk of MI and death in a nationwide cohort of subjects diagnosed with Alzheimer's dementia. These associations were stronger with increasing ChEI dose.
authors.affiliation: Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umeå University, Umeå 90185, Sweden. peter.nordstrom@germed.umu.se
authors.forename: Peter
authors.initials: P
authors.lastname: Nordström
authors.forename: Dorota
authors.initials: D
authors.lastname: Religa
authors.forename: Anders
authors.initials: A
authors.lastname: Wimo
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.forename: Maria
authors.initials: M
authors.lastname: Eriksdotter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000401:mortality; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality / Q000517:prevention & control*; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D002800:Cholinesterase Inhibitors
keywords: Alzheimer's dementia; Choline esterase inhibitors; Myocardial infarction