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Published in: CNS Drugs 5/2010

01-05-2010 | Original Research Article

Predictive factors of discontinuation and switch of cholinesterase inhibitors in community-dwelling patients with Alzheimer’s disease

A 2-year prospective, multicentre, cohort study

Authors: Dr Virginie Gardette, Sandrine Andrieu, Maryse Lapeyre-Mestre, Nicola Coley, Christelle Cantet, Pierre-Jean Ousset, Alain Grand, Jean-Louis Monstastruc, Bruno Vellas

Published in: CNS Drugs | Issue 5/2010

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Abstract

Background: The efficacy of cholinesterase inhibitors (ChEIs), especially over the long term, is still under discussion. There is a lack of data concerning the optimal drug treatment duration and the reasons for discontinuation, particularly outside the clinical trial setting.
Objective: To identify predictive factors of discontinuation and switch of ChEIs in a real-world setting.
Methods: A multicentre cohort study of 686 patients with mild-to-moderate ambulatory Alzheimer’s disease who were diagnosed in 16 Alzheimer’s disease expert centres in 2000–2 and who were assessed twice yearly for 2 years. The main outcome measure was ChEI discontinuation and switch (analysed using Cox survival analyses).
Results: After 2 years, of the 611 subjects treated with a ChEI at baseline, 100 subjects had switched or discontinued ChEI therapy (incidence rate 12.7 [95% CI 10.2, 15.2] per 100 person-years). The incidences of switching and discontinuation were 9.2 (95% CI 7.0, 11.3) and 3.6 (95% CI 2.3, 4.8) per 100 person-years, respectively. In the multivariate analysis, predictive factors for switching were an ineffective ChEI dose (adjusted hazard ratio [HRa] = 6.91, 95% CI 3.08, 15.49), rapid cognitive decline (HRa = 4.10, 95% CI 1.85, 9.05), hospitalization unrelated to Alzheimer’s disease (HRa = 2.33,95% CI 1.07, 5.09) and anxiety (HRa= 2.08, 95% CI 1.16, 3.73). Predictive factors of discontinuation were: hospitalization related (HRa = 9.14, 95% CI 2.69, 31.07) or unrelated (HRa = 4.23, 95% CI 1.54, 11.59) to Alzheimer’s disease, use of an anticholinergic drug (HRa = 4.26, 95% CI 1.46, 12.45) and weight loss (HRa = 3.77, 95% CI 1.15, 12.33).
Conclusions: This study highlights four types of predictors of switch or discontinuation, reflecting disease progression, reconsideration of ChEI benefits, adverse drug reactions to ChEIs and inappropriate concurrent use of anticholinergic drugs. Attention should be paid to anticholinergic agents and prescribers should be given better information about these drugs.
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Metadata
Title
Predictive factors of discontinuation and switch of cholinesterase inhibitors in community-dwelling patients with Alzheimer’s disease
A 2-year prospective, multicentre, cohort study
Authors
Dr Virginie Gardette
Sandrine Andrieu
Maryse Lapeyre-Mestre
Nicola Coley
Christelle Cantet
Pierre-Jean Ousset
Alain Grand
Jean-Louis Monstastruc
Bruno Vellas
Publication date
01-05-2010
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 5/2010
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.2165/11318010-000000000-00000

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