• Online Features  This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (38)  • Contact me when this article is cited  Related Content  • Related letters  • Related article  • Similar articles in this journal  Topic Collections  • Aging/ Geriatrics  • Neurology  • Dementias  • Psychiatry  • Psychopharmacology  • Cardiovascular System  • Surgery  • Surgical Interventions  • Orthopedic Surgery  • Arrhythmias  • Drug Therapy  • Adverse Effects  • Alert me on articles by topic  Social Bookmarking   What's this?

A Population-Based Cohort Study

Sudeep S. Gill, MD, MSc; Geoffrey M. Anderson, MD, PhD; Hadas D. Fischer, MD; Chaim M. Bell, MD, PhD; Ping Li, PhD; Sharon-Lise T. Normand, PhD; Paula A. Rochon, MD, MPH

Arch Intern Med. 2009;169(9):867-873.

Background  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.

Methods  In a population-based cohort study, we 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. We identified 19 803 community-dwelling older adults with dementia who were prescribed cholinesterase inhibitors and 61 499 controls who were not.

Results  Hospital visits for syncope were more frequent in people receiving cholinesterase inhibitors than in controls (31.5 vs 18.6 events per 1000 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 1000 person-years; HR, 1.69; 95% CI, 1.32-2.15), permanent pacemaker insertion (4.7 vs 3.3 events per 1000 person-years; HR, 1.49; 95% CI, 1.12-2.00), and hip fracture (22.4 vs 19.8 events per 1000 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.

Conclusions  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.

Author Affiliations: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada (Drs Gill, Anderson, Fischer, Bell, Li, and Rochon); Department of Medicine, Queen's University, Kingston, Ontario (Dr Gill); Departments of Medicine and Health Policy, Management, and Evaluation, University of Toronto, Toronto (Drs Anderson, Bell, and Rochon); and Harvard Medical School and Harvard School of Public Health, Boston, Massachusetts (Dr Normand).

CiteULike    Connotea    Delicious    Digg    Facebook    Reddit    Technorati    Twitter     What's this?

RELATED LETTERS

Adverse Events in Patients Receiving Cholinesterase Inhibitors Due to Dissimilar Follow-up Periods
Mark Chan
Arch Intern Med. 2009;169(18):1724.
EXTRACT | FULL TEXT  

Adverse Events in Patients Receiving Cholinesterase Inhibitors Due to Dissimilar Follow-up Periods—Reply
Sudeep S. Gill, Chaim M. Bell, and Paula A. Rochon
Arch Intern Med. 2009;169(18):1724-1725.
EXTRACT | FULL TEXT  

RELATED ARTICLE

In This Issue of Archives of Internal Medicine
Arch Intern Med. 2009;169(9):827.
FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Review: in people with dementia, cholinesterase inhibitors may increase syncope and memantine may reduce fractures
Hartikainen and Bell
Evid. Based Ment. Health 2011;14:111-111.
FULL TEXT  

Falls in the elderly: Spectrum and prevention
Al-Aama
cfp 2011;57:771-776.
ABSTRACT | FULL TEXT  

Dementia and Hip Fractures: Development of a Pathogenic Framework for Understanding and Studying Risk
Friedman et al.
Geriatric Orthopaedic Surgery & Rehabilitation 2010;1:52-62.
 

What's new in treating older adults?
MESSINGER-RAPPORT
Cleveland Clinic Journal of Medicine 2010;77:770-790.
ABSTRACT | FULL TEXT  

Randomized, Placebo-Controlled, Clinical Trial of Donepezil in Vascular Dementia: Differential Effects by Hippocampal Size
Roman et al.
Stroke 2010;41:1213-1221.
ABSTRACT | FULL TEXT  

Cautionary Tales in the Interpretation of Clinical Studies Involving Older Persons
Scott and Guyatt
Arch Intern Med 2010;170:587-595.
ABSTRACT | FULL TEXT  

Adverse Events in Patients Receiving Cholinesterase Inhibitors Due to Dissimilar Follow-up Periods
Chan
Arch Intern Med 2009;169:1724-1724.
FULL TEXT  

Adverse Events in Patients Receiving Cholinesterase Inhibitors Due to Dissimilar Follow-up Periods--Reply
Gill et al.
Arch Intern Med 2009;169:1724-1725.
FULL TEXT