Cholinesterase inhibitors are commonly prescribed to treat dementia, but their adverse effect profile has received little attention.  These drugs can provoke symptomatic bradycardia and syncope, which may lead to permanent pacemaker insertion.  Drug-induced syncope may also precipitate fall-related injuries, including hip fracture.

In a population-based cohort study, the authors investigated the relationship between cholinesterase inhibitor use and syncope-related outcomes using health care databases from Ontario, Canada, with accrual from April 1, 2002, to March 31, 2004.  They identified 19,803 community-dwelling older adults with dementia who were prescribed cholinesterase inhibitors and 61,499 controls who were not.

Hospital visits for syncope were more frequent in people receiving cholinesterase inhibitors than in controls (31.5 vs 18.6 events per 1,000 person-years; adjusted hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.57-1.98).  Other syncope-related events were also more common among people receiving cholinesterase inhibitors compared with controls: hospital visits for bradycardia (6.9 vs 4.4 events per 1,000 person-years; HR, 1.69; 95% CI, 1.32-2.15), permanent pacemaker insertion (4.7 vs 3.3 events per 1,000 person-years; HR, 1.49; 95% CI, 1.12-2.00), and hip fracture (22.4 vs 19.8 events per 1,000 person-years; HR, 1.18; 95% CI, 1.04-1.34).  Results were consistent in additional analyses in which subjects were either matched on their baseline comorbidity status or matched using propensity scores.

Use of cholinesterase inhibitors is associated with increased rates of syncope, bradycardia, pacemaker insertion, and hip fracture in older adults with dementia.  The risk of these previously underrecognized serious adverse events must be weighed carefully against the drugs' generally modest benefits.