There are currently four drugs approved for Alzheimer's disease and related disorders. While these medications improve symptoms, they have no substantial impact on disease course. The use of Alzheimer's medications has increased dramatically over the past 20 years. Despite their widespread use, the safety of these medications in a real-world setting remains unclear. With an aging population and increasing use of these medications, there is thus an urgent need to evaluate their safety. To do so, we will study all patients diagnosed with Alzheimer's within the CPRD between April 1997 and March 2017. We will then compare the rates of serious side effects (irregular heartbeats, fainting, severe respiratory symptoms, bleeding ulcers, and death) among those who receive these drugs and those who do not. We will also examine if risks increase with longer duration of treatment or if risks differ by type of Alzheimer's patient (e.g. men vs. women or disease sub-type). In addition, we will describe patterns of medication use, specifically which drugs are started, switched, continued, and stopped. This will be the largest study of Alzheimer's drugs, with up to 20 years of follow-up that covers the entire period these medications have been available.
Objective: Despite the frequent and increasing use of cholinesterase inhibitors (ChEI) and memantine to manage Alzheimer's disease and related disorders, the safety of these medications in a real-world setting remains unclear. Our primary objective is to compare the risk of cardiac arrhythmias among Alzheimer's patients receiving either a ChEI or memantine to that in Alzheimer's patients unexposed to these medications. Secondary objectives include comparing the risks of syncope, chronic obstructive pulmonary disease exacerbations, gastrointestinal bleeding, and mortality, and describing characteristics associated with treatment persistence and patterns of drug use. Methods: We will assemble a cohort of all patients diagnosed with Alzheimer's within the CPRD between April 1998 and March 2017 with at least one year of CPRD history prior to cohort entry. Data analysis: Our nested case-control analysis will use risk-set sampling, and conditional logistic regression models will be used to estimate hazard ratios of ChEI or memantine use versus non-use for each adverse event. All models will be adjusted for demographic, clinical and lifestyle variables, and use of other medications. Patterns of drug utilization, including initiation, persistence and switching will also be examined.
Bradyarrhythmia; Supraventricular tachyarrhythmia; Atrial fibrillation/flutter; Ventricular tachycardia or ventricular fibrillation; Syncope; Chronic obstructive pulmonary disease;
Gastrointestinal bleeding; Drug utilization; Neuropsychiatric symptoms.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Machelle Wilchesky - Corresponding Applicant - McGill University
Edeltraut Kroger - Collaborator - McGill University
Jacques Benisty - Collaborator - Not from an Organisation
Kathleen Andersen - Collaborator - McGill University
Kristian Filion - Collaborator - McGill University
Nathalie Champoux - Collaborator - University Of Montreal
pauline reynier - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Pierre Ernst - Collaborator - McGill University
Robert Platt - Collaborator - McGill University
Roland Grad - Collaborator - McGill University
HES Admitted Patient Care;HES Admitted Patient Care;ONS Death Registration Data;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Patient Level Index of Multiple Deprivation