The influence of cholinesterase inhibitor therapy for dementia on risk of cardiac pacemaker insertion: a retrospective, population-based, health administrative databases study in Ontario, Canada.
BACKGROUND
Cholinesterase inhibitors are used to treat the symptoms of dementia and can theoretically cause bradycardia. Previous studies suggest that patients taking these medications have an increased risk of undergoing pacemaker insertion. Since these drugs have a marginal impact on patient outcomes, it might be preferable to change drug treatment rather than implant a pacemaker. This population-based study determined the association of people with dementia exposed to cholinesterase inhibitor medication and pacemaker insertion.


METHODS
We used data from the Ontario health administrative databases from January 1, 1993 to June 30, 2012. We included all community-dwelling seniors who had a code for dementia and were exposed to cholinesterase inhibitors (donezepil, galantamine, and rivastigmine) and/or drugs used to treat co-morbidities of hypertension, diabetes, depression and hypothyroidism. We controlled for exposure to anti-arrhythmic drugs. Observation started at first exposure to any medication and continued until the earliest of pacemaker insertion, death, or end of study.


RESULTS
2,353,909 people were included with 96,000 (4.1%) undergoing pacemaker insertion during the observation period. Case-control analysis showed that pacemaker patients were less likely to be coded with dementia (unadjusted OR 0.42 [95%CI 0.41-0.42]) or exposed to cholinesterase inhibitors (unadjusted OR 0.39 [95%CI 0.37-0.41]). That Cohort analysis showed patients with dementia taking cholinesterase inhibitors had a decreased risk of pacemaker insertion (unadj-HR 0.58 [0.55-0.61]). Adjustment for patient age, sex, and other medications did not notably change results, as did restricting the analysis to incident users.


CONCLUSIONS
Patients taking cholinesterase inhibitors rarely undergo, and have a significantly reduced risk of, cardiac pacemaker insertion.
Division of Geriatric Medicine, Department of Medicine, University of Ottawa, The Ottawa Hospital, Box 678, 1053 Carling Avenue, Ottawa, Ontario, K1Y 4E9, Canada. allenhuang@toh.on.ca.
Allen R
AR
Huang
Arrhythmia Service, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, K1Y 4 W7, Canada. credpath@ottawaheart.ca.
Calum J
CJ
Redpath
Department of Epidemiology & Community Medicine, University of Ottawa; Ottawa Hospital Research Institute; ICES uOttawa, The Ottawa Hospital, ASB1-003, 1053 Carling Avenue, Ottawa, Ontario, K1Y 4E9, Canada. cvanwalraven@ohri.ca.
Carl
C
van Walraven
D000368:Aged; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D015897:Comorbidity; D016208:Databases, Factual; D003704:Dementia / Q000150:complications / Q000188:drug therapy*; D000077265:Donepezil; D005260:Female; D005702:Galantamine / Q000627:therapeutic use; D006302:Health Services Research; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D008297:Male; D009864:Ontario; D010138:Pacemaker, Artificial; D010880:Piperidines / Q000627:therapeutic use; D019919:Prosthesis Implantation / Q000009:adverse effects*; D012189:Retrospective Studies; D012306:Risk; D000068836:Rivastigmine / Q000627:therapeutic use
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D005702:Galantamine; D000077265:Donepezil; D000068836:Rivastigmine