Cholinesterase inhibitors are associated with large reductions in hospitalization for cardiovascular events and mortality in patients with Alzheimer’s dementia and heart failure

Abstract

AbstractIntroductionCholinesterase inhibitors (ChEIs) are approved for treatment of Alzheimer’s dementia (AD). ChEIs inhibit the enzyme acetylcholinesterase, increasing the duration of action of acetylcholine in the central and peripheral nervous systems. ChEIs are known to be anti‐inflammatory and to have negative chronotropic effects. Observational studies by us and other groups have indeed shown an association with use of ChEIs in AD with lower risk of death and cardiovascular events (CVD) including myocardial infarction, heart failure (HF), and stroke. We next wanted to investigate whether ChEI treatment in AD patients with HF is associated with reduced risk for mortality and for hospitalization due to CVD.MethodsData from the Swedish registry for dementia disorders, SveDem,was linked to the Patient‐, Prescribed Drug‐ and Cause of death registries. In a propensity score (PS) matched cohort of patients with AD and HF, the association between ChEI use and all‐cause death or hospitalization due to CVD was examined with Cox proportional hazards models.ResultsThe PS matched cohort included 455 patients with HF prior to the AD diagnosis with ChEI and 455 non‐ChEI users. During a median follow‐up time of 2.14 years, 549 deaths occurred. Compared to non‐users, ChEI use was associated with 21% lower risk of death (adjusted HR 0.79; 0.66‐0.96). Galantamine and donepezil (0.64; CI 0.47‐0.87 and 0.80; CI 0.64‐0.98) but not rivastigmine (0.96; CI 0.73‐1.28) were associated with lower risk of death. Any ChEI use was associated with a 47% (CI 0.38‐0.75) reduction in risk of hospitalization due to HF and a 52% reduction (CI 0.32‐072) among donepezil‐users.ConclusionsThis study supports previous reports that treatment with ChEIs in AD is associated with reduced mortality risk. We here show that this association is also found in patients with HF and AD but with differential effects among the ChEIs. Further studies are needed to elucidate the mechanisms. The study also showed a substantial reduction in hospitalization due to CVD. Our results highlight the impact of cardiovascular comorbidities in AD which need to be considered in clinical trials as would the impact of the baseline treatment with ChEIs in new anti‐dementia drug trials.