Cholinesterase inhibitors and hospitalization for bradycardia: a population-based study.
BACKGROUND
Cholinesterase inhibitors are commonly used to treat dementia. These drugs enhance the effects of acetylcholine, and reports suggest they may precipitate bradycardia in some patients. We aimed to examine the association between use of cholinesterase inhibitors and hospitalization for bradycardia.


RESULTS
We examined the health care records of more than 1.4 million older adults using a case-time-control design, allowing each individual to serve as his or her own control. Case patients were residents of Ontario, Canada, aged 67 y or older hospitalized for bradycardia between January 1, 2003 and March 31, 2008. Control patients (3:1) were not hospitalized for bradycardia, and were matched to the corresponding case on age, sex, and a disease risk index. All patients had received cholinesterase inhibitor therapy in the 9 mo preceding the index hospitalization. We identified 1,009 community-dwelling older persons hospitalized for bradycardia within 9 mo of using a cholinesterase inhibitor. Of these, 161 cases informed the matched analysis of discordant pairs. Of these, 17 (11%) required a pacemaker during hospitalization, and six (4%) died prior to discharge. After adjusting for temporal changes in drug utilization, hospitalization for bradycardia was associated with recent initiation of a cholinesterase inhibitor (adjusted odds ratio [OR] 2.13, 95% confidence interval [CI] 1.29-3.51). The risk was similar among individuals with pre-existing cardiac disease (adjusted OR 2.25, 95% CI 1.18-4.28) and those receiving negative chronotropic drugs (adjusted OR 2.34, 95% CI 1.16-4.71). We found no such association when we replicated the analysis using proton pump inhibitors as a neutral exposure. Despite hospitalization for bradycardia, more than half of the patients (78 of 138 cases [57%]) who survived to discharge subsequently resumed cholinesterase inhibitor therapy.


CONCLUSIONS
Among older patients, initiation of cholinesterase inhibitor therapy was associated with a more than doubling of the risk of hospitalization for bradycardia. Resumption of therapy following discharge was common, suggesting that the cardiovascular toxicity of cholinesterase inhibitors is underappreciated by clinicians.
Park-Wyllie
Laura Y
LY
Department of Family and Community Medicine, St. Michael's Hospital, Ontario, Canada. parkwylliel@smh.toronto.on.ca
Mamdani
Muhammad M
MM
Li
Ping
P
Gill
Sudeep S
SS
Laupacis
Andreas
A
Juurlink
David N
DN
D000368:Aged; D000369:Aged, 80 and over; D001919:Bradycardia / Q000139:chemically induced* / Q000401:mortality / Q000628:therapy; D002170:Canada; D016022:Case-Control Studies; D002800:Cholinesterase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D003704:Dementia / Q000188:drug therapy; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male
D002800:Cholinesterase Inhibitors