title: Use of rivastigmine or galantamine and risk of adverse cardiac events: a database study from the Netherlands.
abstract: BACKGROUND
  Two cholinesterase inhibitors (ChEIs), rivastigmine and galantamine, are used to treat Alzheimer disease in the Netherlands. Several adverse cardiac events have been reported for these medications.
  
  
  OBJECTIVE
  We aimed to assess if the use of ChEIs increased the risk of cardiac events in the Netherlands.
  
  
  METHODS
  A cohort crossover study of the PHARMO Record Linking System database included patients who initiated ChEIs at age 50 years or older, had at least 1 dispensing of a ChEI drug between 1998 and 2008, a 1-year history in PHARMO, and 1 subsequent dispensing of any medication. Two outcomes were assessed: a first hospitalization for syncope or atrioventricular block. Poisson and Cox regression were used to calculate incidence densities and hazard ratios for cardiac events during periods with ChEI use, compared with periods without ChEI use.
  
  
  RESULTS
  During the complete observation period of 8.9 years (interquartile range 6.7 to 10.2) there were 132 first hospitalizations for atrioventricular block and 17 first hospitalizations for syncope among 3358 patients. The adjusted incidence densities were significantly increased during ChEI exposure for syncope and atrioventricular block, when compared with the background incidence densities in the roughly 5 years before the last year before ChEI initiation. However, when exposed periods were compared with the unexposed periods 1 year before ChEI initiation and times after exposure, the adjusted hazard ratios remained increased for syncope and atrioventricular block, but increases were not significant anymore.
  
  
  CONCLUSIONS
  Exposure to ChEIs might increase the risk of adverse cardiac events, but small numbers of cases limit conclusions about the risk in this population and research on larger study samples is needed.
authors.affiliation: Centre d'excellence sur le vieillissement de Québec, Centre de recherche FRQ-S du CHU universitaire de Québec, Québec, Canada. edeltraut.kroger.cha@ssss.gouv.qc.ca
authors.forename: Edeltraut
authors.initials: E
authors.lastname: Kröger
authors.forename: Mieke
authors.initials: M
authors.lastname: Berkers
authors.forename: Pierre-Hugues
authors.initials: PH
authors.lastname: Carmichael
authors.forename: Patrick
authors.initials: P
authors.lastname: Souverein
authors.forename: Rob
authors.initials: R
authors.lastname: van Marum
authors.forename: Toine
authors.initials: T
authors.lastname: Egberts
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy*; D054537:Atrioventricular Block / Q000139:chemically induced / Q000453:epidemiology; D002800:Cholinesterase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D018592:Cross-Over Studies; D016208:Databases, Factual; D005260:Female; D005702:Galantamine / Q000009:adverse effects* / Q000627:therapeutic use; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D008297:Male; D009426:Netherlands; D048448:Phenylcarbamates / Q000009:adverse effects* / Q000627:therapeutic use; D016012:Poisson Distribution; D016016:Proportional Hazards Models; D012306:Risk; D000068836:Rivastigmine; D013575:Syncope / Q000139:chemically induced / Q000453:epidemiology
chemical_list: D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; D005702:Galantamine; D000068836:Rivastigmine