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

OBJECTIVES: To evaluate the cardiovascular (CV) effectsof acetylcholinesterase inhibitors (AChEIs) in individualswith dementiaDESIGN: Systematic review and meta-analysis.SETTING: Two authors independently searched majorelectronic databases from inception until June 17, 2017,for longitudinal (without a control group) and cohort(with a control group) studies reporting CV outcomes inrelation to AChEIs. Randomized controlled trials wereexcluded because they included relatively healthy subjects.PARTICIPANTS: Individuals with dementia and controls.MEASUREMENTS: Changes in CV parameters were sum-marized using standardized mean differences (SMDs) with95% confidence intervals (CIs). E vent rates were used toassess incidence of hypertension and bradycardia. Inci-dence of CV events in demented patients versus in healthycontrols were compared using hazard ratios (HRs).RESULTS: Of 4,588 initial hits, 31 studies including258,540 individuals with dementia and 2,246,592 controlswere analyzed. In longitudinal and open-label studies,AChEIs were associated with a significantly greater inci-dence of hypertension (n51,573, 4%, 95% CI52-8%,I2547%) and bradycardia (n513,703, 2%, 95% CI51-6%, I2598%). AChEIs were associated with a decrease inheart rate (SMD5-1.77, 95% CI5-3.58-0.03, I2578%)and an increase in PR interval (SMD50.10, 95%CI50.008-0.19, I253%) from baseline. During a medianfollow-up of 116 weeks, AChEIs were associated with asignificantly lower risk of CV events (stroke, acute coronarysyndrome, CV mortality; HR50.63, 95% CI50.45-0.88,I2518%), without a significantly greater risk of bradycar-dic events (HR51.40, 95% CI50.76-2.59, I2598%).CONCLUSION: AChEI therapy may be associated withnegative chronotropic and hypertensive effects but alsowith lower risk of CV events.