Abstract
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. 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. 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.
Highlights
Cholinesterase inhibitors such as donepezil, rivastigmine, and galantamine are widely prescribed to improve cognitive function in patients with Alzheimer disease—a condition expected to quadruple in prevalence over the 50 y [1]
Resumption of therapy following discharge was common, suggesting that the cardiovascular toxicity of cholinesterase inhibitors is underappreciated by clinicians
Between January 1, 2003 and March 31, 2008, we identified 27,333 hospitalizations for bradycardia among Ontario residents 67 y and older
Summary
Cholinesterase inhibitors such as donepezil, rivastigmine, and galantamine are widely prescribed to improve cognitive function in patients with Alzheimer disease—a condition expected to quadruple in prevalence over the 50 y [1]. Symptoms of cholinergic excess are often nonspecific and include gastrointestinal upset, diarrhea, hypersalivation, and muscle cramps In severe instances, these drugs can increase vagal tone and thereby precipitate bradycardia. 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. A common treatment for Alzheimer disease is a class of drug called an acetylcholinesterase inhibitor or cholinesterase inhibitor These include donepezil (brand name Aricept), rivastigmine (marketed as Exelon and Exelon Patch), and galantamine (branded Razadyne). In about 50% of patients they delay the worsening of symptoms for between six months and a year, a small number of patients may benefit more They can have unpleasant side effects, which may include diarrhoea and muscle cramps
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