Skip to main content
Top
Published in: BMC Neurology 1/2015

Open Access 01-12-2015 | Research article

The influence of cholinesterase inhibitor therapy for dementia on risk of cardiac pacemaker insertion: a retrospective, population-based, health administrative databases study in Ontario, Canada

Authors: Allen R Huang, Calum J Redpath, Carl van Walraven

Published in: BMC Neurology | Issue 1/2015

Login to get access

Abstract

Background

Cholinesterase inhibitors are used to treat the symptoms of dementia and can theoretically cause bradycardia. Previous studies suggest that patients taking these medications have an increased risk of undergoing pacemaker insertion. Since these drugs have a marginal impact on patient outcomes, it might be preferable to change drug treatment rather than implant a pacemaker. This population-based study determined the association of people with dementia exposed to cholinesterase inhibitor medication and pacemaker insertion.

Methods

We used data from the Ontario health administrative databases from January 1, 1993 to June 30, 2012. We included all community-dwelling seniors who had a code for dementia and were exposed to cholinesterase inhibitors (donezepil, galantamine, and rivastigmine) and/or drugs used to treat co-morbidities of hypertension, diabetes, depression and hypothyroidism. We controlled for exposure to anti-arrhythmic drugs. Observation started at first exposure to any medication and continued until the earliest of pacemaker insertion, death, or end of study.

Results

2,353,909 people were included with 96,000 (4.1%) undergoing pacemaker insertion during the observation period. Case–control analysis showed that pacemaker patients were less likely to be coded with dementia (unadjusted OR 0.42 [95%CI 0.41-0.42]) or exposed to cholinesterase inhibitors (unadjusted OR 0.39 [95%CI 0.37-0.41]). That Cohort analysis showed patients with dementia taking cholinesterase inhibitors had a decreased risk of pacemaker insertion (unadj-HR 0.58 [0.55-0.61]). Adjustment for patient age, sex, and other medications did not notably change results, as did restricting the analysis to incident users.

Conclusions

Patients taking cholinesterase inhibitors rarely undergo, and have a significantly reduced risk of, cardiac pacemaker insertion.
Literature
1.
2.
go back to reference Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, et al. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005;366:2112–7.CrossRefPubMedPubMedCentral Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, et al. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005;366:2112–7.CrossRefPubMedPubMedCentral
3.
go back to reference Grutzendler J, Morris JC. Cholinesterase inhibitors for Alzheimer’s disease. Drugs. 2001;61:41–52.CrossRefPubMed Grutzendler J, Morris JC. Cholinesterase inhibitors for Alzheimer’s disease. Drugs. 2001;61:41–52.CrossRefPubMed
4.
go back to reference Rogers SL, Doody RS, Pratt RD, Ieni JR. Long-term efficacy and safety of donepezil in the treatment of Alzheimer’s disease: final analysis of a US multicentre open-label study. Eur Neuropsychopharmacol. 2000;10:195–203.CrossRefPubMed Rogers SL, Doody RS, Pratt RD, Ieni JR. Long-term efficacy and safety of donepezil in the treatment of Alzheimer’s disease: final analysis of a US multicentre open-label study. Eur Neuropsychopharmacol. 2000;10:195–203.CrossRefPubMed
5.
go back to reference Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev. 2006;25(1):CD005593. Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev. 2006;25(1):CD005593.
6.
go back to reference Suleyman T, Tevfik P, Abdulkadir G, Ozlem S. Complete atrioventricular block and ventricular tachyarrhythmia associated with donepezil. Emerg Med J. 2006;23:641–2.CrossRefPubMedPubMedCentral Suleyman T, Tevfik P, Abdulkadir G, Ozlem S. Complete atrioventricular block and ventricular tachyarrhythmia associated with donepezil. Emerg Med J. 2006;23:641–2.CrossRefPubMedPubMedCentral
7.
go back to reference Bordier P, Garrigue S, Barold SS, Bressolles N, Lanusse S, Clementy J. Significance of syncope in patients with Alzheimer’s disease treated with cholinesterase inhibitors. Europace. 2003;5:429–31.CrossRefPubMed Bordier P, Garrigue S, Barold SS, Bressolles N, Lanusse S, Clementy J. Significance of syncope in patients with Alzheimer’s disease treated with cholinesterase inhibitors. Europace. 2003;5:429–31.CrossRefPubMed
8.
go back to reference Shepherd G, Klein-Schwartz W, Edwards R. Donepezil overdose: a tenfold dosing error. Ann Pharmacother. 1999;33:812–5.CrossRefPubMed Shepherd G, Klein-Schwartz W, Edwards R. Donepezil overdose: a tenfold dosing error. Ann Pharmacother. 1999;33:812–5.CrossRefPubMed
9.
go back to reference Calvo-Romero JM, Ramos-Salado JL. [Symptomatic sinus bradycardia associated with donepezil]. Rev Neurol. 1999;28:1070–2.PubMed Calvo-Romero JM, Ramos-Salado JL. [Symptomatic sinus bradycardia associated with donepezil]. Rev Neurol. 1999;28:1070–2.PubMed
10.
go back to reference Park-Wyllie LY, Mamdani MM, Li P, Gill SS, Laupacis A, Juurlink DN. Cholinesterase inhibitors and hospitalization for bradycardia: a population-based study. PLoS Med. 2009;6:e1000157.CrossRefPubMedPubMedCentral Park-Wyllie LY, Mamdani MM, Li P, Gill SS, Laupacis A, Juurlink DN. Cholinesterase inhibitors and hospitalization for bradycardia: a population-based study. PLoS Med. 2009;6:e1000157.CrossRefPubMedPubMedCentral
11.
go back to reference Hernandez RK, Farwell W, Cantor MD, Lawler EV. Cholinesterase inhibitors and incidence of bradycardia in patients with dementia in the veterans affairs new England healthcare system. J Am Geriatr Soc. 2009;57:1997–2003.CrossRefPubMed Hernandez RK, Farwell W, Cantor MD, Lawler EV. Cholinesterase inhibitors and incidence of bradycardia in patients with dementia in the veterans affairs new England healthcare system. J Am Geriatr Soc. 2009;57:1997–2003.CrossRefPubMed
12.
go back to reference Kroger E, Berkers M, Carmichael PH, Souverein P, van Marum R, Egberts T. Use of rivastigmine or galantamine and risk of adverse cardiac events: a database study from the Netherlands. Am J Geriatr Pharmacother. 2012;10:373–80.CrossRefPubMed Kroger E, Berkers M, Carmichael PH, Souverein P, van Marum R, Egberts T. Use of rivastigmine or galantamine and risk of adverse cardiac events: a database study from the Netherlands. Am J Geriatr Pharmacother. 2012;10:373–80.CrossRefPubMed
13.
go back to reference Gill SS, Anderson GM, Fischer HD, Bell CM, Li P, Normand SL, et al. Syncope and its consequences in patients with dementia receiving cholinesterase inhibitors: a population-based cohort study. Arch Intern Med. 2009;169:867–73.CrossRefPubMed Gill SS, Anderson GM, Fischer HD, Bell CM, Li P, Normand SL, et al. Syncope and its consequences in patients with dementia receiving cholinesterase inhibitors: a population-based cohort study. Arch Intern Med. 2009;169:867–73.CrossRefPubMed
14.
go back to reference Ames D, Kaduszkiewicz H, van den Bussche H, Zimmermann T, Birks J, Ashby D. For debate: is the evidence for the efficacy of cholinesterase inhibitors in the symptomatic treatment of Alzheimer’s disease convincing or not? Int Psychogeriatr. 2008;20:259–92.PubMed Ames D, Kaduszkiewicz H, van den Bussche H, Zimmermann T, Birks J, Ashby D. For debate: is the evidence for the efficacy of cholinesterase inhibitors in the symptomatic treatment of Alzheimer’s disease convincing or not? Int Psychogeriatr. 2008;20:259–92.PubMed
15.
go back to reference Wilchesky M, Tamblyn RM, Huang A. Validation of diagnostic codes within medical services claims. J Clin Epidemiol. 2004;57:131–41.CrossRefPubMed Wilchesky M, Tamblyn RM, Huang A. Validation of diagnostic codes within medical services claims. J Clin Epidemiol. 2004;57:131–41.CrossRefPubMed
16.
go back to reference Taylor J, Fillenbaum GG, Ezell ME. The accuracy of medicare claims data in identifying Alzheimer’s disease. J Clin Epidemiol. 2002;55:929–37.CrossRefPubMed Taylor J, Fillenbaum GG, Ezell ME. The accuracy of medicare claims data in identifying Alzheimer’s disease. J Clin Epidemiol. 2002;55:929–37.CrossRefPubMed
17.
go back to reference Williams EMV. A classification of antiarrhythmic actions reassessed after a decade of new drugs. J Clin Pharmacol. 1984;24:129–47.CrossRef Williams EMV. A classification of antiarrhythmic actions reassessed after a decade of new drugs. J Clin Pharmacol. 1984;24:129–47.CrossRef
18.
go back to reference Rosenbaum PR. Optimal matching for observational studies. J Am Stat Assoc. 1989;84:1024–32.CrossRef Rosenbaum PR. Optimal matching for observational studies. J Am Stat Assoc. 1989;84:1024–32.CrossRef
19.
go back to reference Stokes ME, Davis CS, Koch GG. Conditional logisitic regression. In: Categorical data analysis using the SAS system. 1st ed. Cary, N.C.: SAS Institute Inc; 2000. p. 273–322. Stokes ME, Davis CS, Koch GG. Conditional logisitic regression. In: Categorical data analysis using the SAS system. 1st ed. Cary, N.C.: SAS Institute Inc; 2000. p. 273–322.
20.
go back to reference Essebag V, Hadjis T, Platt RW, Pilote L. Amiodarone and the risk of bradyarrhythmia requiring permanent pacemaker in elderly patients with atrial fibrillation and prior myocardial infarction. J Am Coll Cardiol. 2003;41:249–54.CrossRefPubMed Essebag V, Hadjis T, Platt RW, Pilote L. Amiodarone and the risk of bradyarrhythmia requiring permanent pacemaker in elderly patients with atrial fibrillation and prior myocardial infarction. J Am Coll Cardiol. 2003;41:249–54.CrossRefPubMed
21.
go back to reference Essebag V, Reynolds MR, Hadjis T, Lemery R, Olshansky B, Buxton AE, et al. Sex differences in the relationship between amiodarone use and the need for permanent pacing in patients with atrial fibrillation. Arch Intern Med. 2007;167:1648–53.CrossRefPubMedPubMedCentral Essebag V, Reynolds MR, Hadjis T, Lemery R, Olshansky B, Buxton AE, et al. Sex differences in the relationship between amiodarone use and the need for permanent pacing in patients with atrial fibrillation. Arch Intern Med. 2007;167:1648–53.CrossRefPubMedPubMedCentral
22.
go back to reference Gillis AM, Verma A, Talajic M, Nattel S, Dorian P. Canadian Cardiovascular Society atrial fibrillation guidelines 2010: rate and rhythm management. Can J Cardiol. 2011;27:47–59.CrossRefPubMed Gillis AM, Verma A, Talajic M, Nattel S, Dorian P. Canadian Cardiovascular Society atrial fibrillation guidelines 2010: rate and rhythm management. Can J Cardiol. 2011;27:47–59.CrossRefPubMed
23.
go back to reference Epstein AE, DiMarco JP, Ellenbogen KA, Estes III NA, Freedman RA, Gettes LS, et al. ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation. 2012;2013(127):e283–352. Epstein AE, DiMarco JP, Ellenbogen KA, Estes III NA, Freedman RA, Gettes LS, et al. ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation. 2012;2013(127):e283–352.
Metadata
Title
The influence of cholinesterase inhibitor therapy for dementia on risk of cardiac pacemaker insertion: a retrospective, population-based, health administrative databases study in Ontario, Canada
Authors
Allen R Huang
Calum J Redpath
Carl van Walraven
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2015
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-015-0325-1

Other articles of this Issue 1/2015

BMC Neurology 1/2015 Go to the issue