Evaluating the Association between Cholinesterase Inhibitors and Subsequent Cardiovascular Events among Older Patients with Dementia

Background Cholinesterase inhibitors, a class of medications indicated for the treatment of dementia, have been shown to provide a cardioprotective effect in recent in-vitro and in-vivo studies with a mechanism of the vagal influences on the heart and its plausible anti-inflammatory effect. However, whether taking cholinesterase inhibitors is associated with a decreased risk of subsequent cardiovascular events among patients with dementia remains unknown. Purpose The purpose of this study is to determine whether the use of cholinesterase inhibitors decreases the risk of subsequent cardiovascular events among patients aged 50 years or older with dementia in Taiwan Method We will perform a retrospective cohort study using the Two-Million-Sample Longitudinal Health and Welfare Database managed by the Health and Welfare Data Science Center (HWDC) of the Department of Statistics under the Ministry of Health and Welfare in Taiwan. Dementia patients who initiated treatment with cholinesterase inhibitors during January 1, 2001 and December 31, 2010 and had no prior diagnosis of cardiovascular diseases will be enrolled. New cholinesterase inhibitor users will be matched by propensity scores to non-users and follow to determine whether they will have subsequent cardiovascular events. We will use the Poisson regression model to measure the incidence rate ratio (IRR) and use the Cox-proportional hazard regression model to compare time to diagnosis of cardiovascular events between 1) cholinesterase inhibitor users versus nonusers, 2) cholinesterase inhibitor users with the upward dose titration strategy versus the initial maximum dose strategy, 3) cholinesterase inhibitor users with high versus low cumulative dose, and 4) cholinesterase inhibitor users with high medication adherence versus low adherence. Propensity score matching will be used to balance the selected confounders between groups. Anticipated outcomes We expect that cholinesterase inhibitor users will have a lower incidence rate and a lower hazard of subsequent cardiovascular events compared with nonusers. The results will inform physicians and pharmacists about the therapeutic benefits of cholinesterase inhibitor use regarding cardiovascular disease protection, and will ultimately improve treatment outcomes among patients with dementia in Taiwan.