Alzheimer's Disease Drugs Increase Risk of Abnormally Slow Heart Rate

According to the analysis of data from a study of 1.4 million people aged 67 and older, people taking one of several drugs commonly prescribed to treat Alzheimer's disease are more likely to be hospitalized for a potentially serious condition called bradycardia than patients not taking these medications.
The study found that the risk of abnormally slow heart rate is twice as high in those taking drugs to slow Alzheimer's disease.

Cholinesterase inhibitors are commonly prescribed to delay the progression of symptoms such as confusion and long-term memory loss in people with mild to moderate Alzheimer's disease.

The benefits of cholinesterase inhibitors for people with Alzheimer's disease are generally small. Thy do not reverse the effects of dementia and other research suggests that in about half of patients, they delay the worsening of symptoms for between six months to a year, although a minority of patients may benefit more.

Bradycardia is defined as an abnormally slow resting heart rate (under 60 beats per minute). Although it can be asymptomatic, it can also cause fainting, palpitations, shortness of breath, or even death.

The three cholinesterase inhibitors currently approved for use in Canada are donepezil, rivastigmine, and galantamine. Most of the Alzheimer's disease patients whose records were analyzed for the study had been prescribed donepezil.

The results of the study showed that older patients hospitalized with bradycardia were more than twice as likely to have recently started on a cholinesterase inhibitor such as donepezil for Alzheimer's disease compared to those without bradycardia.

The researchers say that as the prevalence of Alzheimer's disease and other forms of dementia increases, more people aged 65 years and older will be treated with a cholinesterase inhibitor.

"It will be increasingly more important to prescribe these drugs judiciously as they carry a risk of serious adverse events," Park-Wyllie says. "A careful clinical evaluation is required before and after initiating these drugs, and they should only be continued when there is a definite positive response."

The potential cardiovascular toxicity of these dementia drugs may be underappreciated by clinicians, Park-Wyllie adds. More than half of the patients who had been hospitalized with bradycardia resumed taking their cholinesterase inhibitor after being discharged.

"Our study provides evidence of the potential adverse effect of cholinesterase inhibitors on heart rate. Health professionals need to reassess the merits of continued therapy in patients who develop bradycardia while taking these drugs," she says.

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References:
1. Park-Wyllie LY, Mamdani MM, Li P, Gill SS, Laupacis A, et al. 2009 Cholinesterase Inhibitors and Hospitalization for Bradycardia: A Population-Based Study. PLoS Med 6(9): e1000157. doi:10.1371/journal.pmed.1000157 .