Background: Cholinesterase inhibitors are approved to treat patients with mild to moderate Alzheimer disease, and are also often used to treat other types of dementia. Their potential for side effects such as bradycardia may be underestimated because initial clinical trials tended to exclude patients with certain cardiovascular disorders. One review found that only 8 percent of patients with Alzheimer disease who were treated with cholinesterase inhibitors would have been eligible to participate. Hernan-dez and colleagues studied the relationship between cholinesterase inhibitor therapy and bradycardia.

The Study: The authors of this population-based cohort study enrolled patients with dementia in the New England Veterans Affairs Healthcare System. Over a two-year period, the incidence of bradycardia was assessed among patients using one of three cholinesterase inhibitors (i.e., donepezil [Aricept], galantamine [Razadyne], and rivastigmine [Exelon]) compared with persons not using these medications. Patients were excluded from the study if they had preexisting bradycardia, sinus syncope, or a pacemaker.

Results: The authors found that 3,198 (28 percent) of the 11,328 patients with dementia had taken cholinesterase inhibitors. Donepezil was most commonly used (90.3 percent), with fewer patients taking galantamine or rivastigmine (10.1 percent and 6.8 percent, respectively, including persons who had used more than one cholinesterase inhibitor). Overall, cholinesterase inhibitors were associated with higher rates of bradycardia (incidence of 0.82 per 1,000 person-days in the treatment group versus 0.47 in the unexposed group; hazard ratio [HR] = 1.4). The greatest risk occurred with higher dosages of donepezil (HR = 1.3 for 10 mg per day; HR = 2.1 for 15 or 20 mg per day). Patients at the greatest risk of bradycardia were those taking beta blockers; those who had fallen after the diagnosis of dementia; and those with a history of myocardial infarction, heart failure, or hypertension.

Conclusion: The authors conclude that patients with dementia who are treated with cholinesterase inhibitors are at greater risk of bradycardia, especially those taking donepezil in a dosage of 15 or 20 mg per day. Closer monitoring of heart rates may be warranted in these patients, especially those with certain high-risk traits.