Cardiovascular Outcomes of Cholinesterase Inhibitors in Individuals with Dementia: A Meta-Analysis and Systematic Review

Objectives: To evaluate the cardiovascular (CV) effects of acetylcholinesterase inhibitors (AChEIs) in individuals with dementia. Design: Systematic review and meta-analysis. Setting: Two authors independently searched major electronic databases from inception until June 17, 2017, for longitudinal (without a control group) and cohort (with a control group) studies reporting CV outcomes in relation to AChEIs. Randomized controlled trials were excluded because they included relatively healthy subjects. Participants: Individuals with dementia and controls. Measurements: Changes in CV parameters were summarized using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Event rates were used to assess incidence of hypertension and bradycardia. Incidence of CV events in demented patients versus in healthy controls were compared using hazard ratios (HRs). Results: Of 4,588 initial hits, 31 studies including 258,540 individuals with dementia and 2,246,592 controls were analyzed. In longitudinal and open-label studies, AChEIs were associated with a significantly greater incidence of hypertension (n=1,573, 4%, 95% CI=2–8%, I2=47%) and bradycardia (n=13,703, 2%, 95% CI=1–6%, I2=98%). AChEIs were associated with a decrease in heart rate (SMD=–1.77, 95% CI=–3.58–0.03, I2=78%) and an increase in PR interval (SMD=0.10, 95% CI=0.008–0.19, I2=3%) from baseline. During a median follow-up of 116 weeks, AChEIs were associated with a significantly lower risk of CV events (stroke, acute coronary syndrome, CV mortality; HR=0.63, 95% CI=0.45–0.88, I2=18%), without a significantly greater risk of bradycardic events (HR=1.40, 95% CI=0.76–2.59, I2=98%). Conclusion: AChEI therapy may be associated with negative chronotropic and hypertensive effects but also with lower risk of CV events. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society