A retrospective study of cholinesterase inhibitors for Alzheimer's disease: cerebrovascular disease as a predictor of patient outcomes

ABSTRACT

Background: Dementia may be caused by Alzheimer's disease (AD), cerebrovascular disease (CVD), or a combination of both. When CVD is associated with dementia, survival is thought to be reduced. It is unclear whether treatment with cholinesterase inhibitors (ChEIs), which has been found to slow disease progression in AD patients, has similar benefits in vascular forms of dementia.

Objectives: The present study was designed to determine whether co-existing CVD is associated with survival or time to nursing home placement (NHP) among AD patients treated with ChEIs. Findings of poorer outcomes in patients with versus without CVD might argue against the use of ChEIs for AD patients in whom CVD co-exists.

Methods: A retrospective cohort study was undertaken using the Régie de l’Assurance Maladie du Québec (RAMQ) databases to examine the time to NHP or death for AD patients aged 66+, with or without CVD, treated with ChEIs between July 1, 2000, and June 30, 2003. Because ChEIs are approved only for AD in Canada, a ChEI prescription was used as a surrogate for an AD diagnosis. Separate analyses were performed for patients with persistent ChEI use and those who discontinued ChEI therapy.

Results: A total of 4428 patients met inclusion criteria for AD with CVD; 13 512 were classified as having AD alone. For the composite endpoint of NHP or death, 1000-day survival rates were lower among AD patients with versus without CVD (p < 0.01), but absolute differences were very small (84 vs. 86% with continuous ChEI use; 77 vs. 78% with discontinuous ChEI therapy). Of the secondary endpoints, time to death was shorter for patients with versus without CVD, but time to NHP did not differ between groups.

Limitations: Results may have been affected by selection (misclassification) bias and between-group differences in smoking, body mass index, and duration of ChEI therapy.

Conclusions: Associations between co-existing CVD and time to NHP or death appeared to be of little clinical relevance among AD patients treated with ChEIs. The lack of difference between AD patients with and without CVD suggests that CVD should not be used as a reason to deny AD patients access to ChEI treatment.

Key words: :

• Administrative database
• Alzheimer's disease
• Cerebrovascular disease
• Cholinesterase inhibitors
• Dementia

Acknowledgements

Declaration of interest: No funding was received for this specific study, but Pharmacoeconomics and Pharmacoepidemiology Research Unit, Centre hospitalier de l’Université de Montréal Research Center – Hôtel-Dieu receives or has received funds for other unrelated research projects from the following manufacturers of cholinesterase inhibitors: Janssen-Ortho, Novartis and Pfizer. JL has worked as a paid consultant and speaker for the same companies. This work was performed as part of the PhD thesis of CC, who is a paid employee of Pfizer.