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

Ahmet Turan Isik; Pinar Soysal; Brendon Stubbs; Marco Solmi; Cristina Basso; Stefania Maggi; Patricia Schofield; Nicola Veronese; Christoph Mueller

doi:10.1111/jgs.15415

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

Ahmet Turan Isik^*, Pinar Soysal, Brendon Stubbs, Marco Solmi, Cristina Basso, Stefania Maggi, Patricia Schofield, Nicola Veronese, Christoph Mueller

^*Corresponding author for this work

School of Nursing and Midwifery

Research output: Contribution to journal › Article › peer-review

Abstract

ObjectivesTo evaluate the cardiovascular (CV) effects of acetylcholinesterase inhibitors (AChEIs) in individuals with dementiaDesignSystematic review and meta‐analysis.SettingTwo 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.ParticipantsIndividuals with dementia and controls.MeasurementsChanges 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).ResultsOf 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%).ConclusionAChEI therapy may be associated with negative chronotropic and hypertensive effects but also with lower risk of CV events.

Original language	English
Pages (from-to)	1805-1811
Number of pages	0
Journal	Journal of the American Geriatrics Society
Volume	66
Issue number	9
Early online date	30 May 2018
DOIs	https://doi.org/10.1111/jgs.15415
Publication status	Published - Sept 2018

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@article{77abd842d3694ca983fe87c7c69e9bd7,

title = "Cardiovascular Outcomes of Cholinesterase Inhibitors in Individuals with Dementia: A Meta‐Analysis and Systematic Review",

abstract = "ObjectivesTo evaluate the cardiovascular (CV) effects of acetylcholinesterase inhibitors (AChEIs) in individuals with dementiaDesignSystematic review and meta‐analysis.SettingTwo 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.ParticipantsIndividuals with dementia and controls.MeasurementsChanges 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).ResultsOf 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%).ConclusionAChEI therapy may be associated with negative chronotropic and hypertensive effects but also with lower risk of CV events.",

author = "Isik, {Ahmet Turan} and Pinar Soysal and Brendon Stubbs and Marco Solmi and Cristina Basso and Stefania Maggi and Patricia Schofield and Nicola Veronese and Christoph Mueller",

year = "2018",

month = sep,

doi = "10.1111/jgs.15415",

language = "English",

volume = "66",

pages = "1805--1811",

journal = "Journal of the American Geriatrics Society",

issn = "0002-8614",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "9",

}

TY - JOUR

T1 - Cardiovascular Outcomes of Cholinesterase Inhibitors in Individuals with Dementia: A Meta‐Analysis and Systematic Review

AU - Isik, Ahmet Turan

AU - Soysal, Pinar

AU - Stubbs, Brendon

AU - Solmi, Marco

AU - Basso, Cristina

AU - Maggi, Stefania

AU - Schofield, Patricia

AU - Veronese, Nicola

AU - Mueller, Christoph

PY - 2018/9

Y1 - 2018/9

N2 - ObjectivesTo evaluate the cardiovascular (CV) effects of acetylcholinesterase inhibitors (AChEIs) in individuals with dementiaDesignSystematic review and meta‐analysis.SettingTwo 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.ParticipantsIndividuals with dementia and controls.MeasurementsChanges 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).ResultsOf 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%).ConclusionAChEI therapy may be associated with negative chronotropic and hypertensive effects but also with lower risk of CV events.

AB - ObjectivesTo evaluate the cardiovascular (CV) effects of acetylcholinesterase inhibitors (AChEIs) in individuals with dementiaDesignSystematic review and meta‐analysis.SettingTwo 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.ParticipantsIndividuals with dementia and controls.MeasurementsChanges 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).ResultsOf 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%).ConclusionAChEI therapy may be associated with negative chronotropic and hypertensive effects but also with lower risk of CV events.

U2 - 10.1111/jgs.15415

DO - 10.1111/jgs.15415

M3 - Article

SN - 0002-8614

VL - 66

SP - 1805

EP - 1811

JO - Journal of the American Geriatrics Society

JF - Journal of the American Geriatrics Society

IS - 9

ER -

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

Abstract

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