Cardiovascular pharmacodynamics of donepezil hydrochloride on the PR and QT intervals in patients with dementia

Igeta, Hirofumi; Suzuki, Yutaro; Tajiri, Misuzu; Someya, Toshiyuki

doi:10.1002/hup.2398

Cited by 18 publications

(16 citation statements)

References 23 publications

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“…After excluding 4,324 papers after title and abstract review, 264 full‐text articles were examined, and 31 studies were \ included in the systematic review with meta‐analysis (22 longitudinal studies without a control group; 9 cohort studies with a control group) (Supplementary Figure S1). Seven of those were open‐label studies . The 22 longitudinal studies included a total of 34 independent cohorts.…”

Section: Resultsmentioning

confidence: 99%

“…Seven of those were open-label studies. [20][21][22][23][24]33,37 The 22 longitudinal studies included a total of 34 independent cohorts.…”

Section: Resultsmentioning

confidence: 99%

“…Study and participant characteristics are summarized in Supplementary Table S2 (longitudinal studies) and Supplementary Table S3 (cohort studies). Altogether, the 31 studies analyzed represented 258,540 individuals with dementia (15,041 in longitudinal studies, 243,499 in cohort studies) and 2,246,592 controls . Approximately one‐third of the participants had AD, and 66.4% had mixed dementia (Supplementary Tables S2 and S3).…”

Section: Resultsmentioning

confidence: 99%

“…Regarding outcomes, hypertension was defined according to objective measurement in 9 studies. [13][14][15][16][23][24][25][26]33 Bradycardia and heart rate changes were evaluated according to objective measurement in 17 studies, 13,[15][16][17]19,[22][23][24][25][26][27][28][29][30][31]33,34 and one study reported data on bradycardia from a database. 32 After a median follow-up of 24 weeks (range 3-463 weeks), AChEI use was associated with a higher proportion of hypertension in 7 studies compared to baseline (1,573 individuals, 4%, 95% CI52-8%, p<.001, I 2 547%) and bradycardia in 12 studies (13,703 participants, 2%, 95% CI51-6%, p<.001, I 2 598%).…”

Section: Longitudinal Studies Reporting On Changes Over Time In CV Oumentioning

confidence: 99%

See 3 more Smart Citations

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

Işık

Soysal

Stubbs

et al. 2018

J American Geriatrics Society

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Section: Resultsmentioning

confidence: 99%

“…Seven of those were open-label studies. [20][21][22][23][24]33,37 The 22 longitudinal studies included a total of 34 independent cohorts.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Longitudinal Studies Reporting On Changes Over Time In CV Oumentioning

confidence: 99%

See 2 more Smart Citations

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

Işık

Soysal

Stubbs

et al. 2018

J American Geriatrics Society

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“…These results could not reflect the pervasive impact of donepezil intervention because some cases had specific disease backgrounds such as unknown sinus sick syndrome, paroxysmal atrial fibrillation, myocardial infarction, or combination therapy with negative chronotropic drugs [ 27 , 31 ]. On the contrary, Isik and Igeta [ 32 , 33 ] reported that donepezil administration did not change QT and QTc interval in patients with AD compared with baseline. In the present study, no significant difference in QT, QTc, QTd, and T peak-end interval was detected after 4 weeks of donepezil intervention.…”

Section: Discussionmentioning

confidence: 99%

Electrocardiogram Changes of Donepezil Administration in Elderly Patients with Ischemic Heart Disease

Wang

An-cai

et al. 2018

Cardiology Research and Practice

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Objective Donepezil, a widely used cholinesterase inhibitor for treating Alzheimer's disease, has been reported to induce bradyarrhythmias and torsade de pointes. In this study, we aimed at determining electrocardiogram changes of donepezil administration in elderly patients with ischemic heart disease, who tend to suffer from cognitive disorders. Methods Sixty patients with ischemic heart disease and mild cognitive impairment were treated with donepezil (5 mg/day) and followed up for at least four weeks. A twenty-four-hour ambulatory electrocardiogram was performed for the analysis of heart rate variability. The ECG parameters including heart rate (HR), PR and RR intervals, QT interval, and QRS duration were recorded at the baseline and after donepezil administration. Results Donepezil administration resulted in significant reduction in mean HR and the lowest HR and prolongation of PR and RR intervals, whereas it had no significant effects on QRS duration and QT parameters including QT, corrected QT interval, QT dispersion, and Tpeak-end interval. HRV analysis showed that donepezil administration significantly improved parasympathetic function, indicated by decreased low/high frequency (LF/HF) ratio and high frequency (HF) components and oscillation of RR intervals. Conclusions These data demonstrated that donepezil administration decreased HR, prolonged PR interval, and increased parasympathetic function without affecting QRS duration and QT intervals, suggesting that it can be used safely in elderly patients with ischemic heart disease.

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Comparative risk of cardiac arrhythmias associated with acetylcholinesterase inhibitors used in treatment of dementias – A narrative review

Huang

Alsabbagh

2020

Pharmacology Res & Perspec

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Donepezil, galantamine, and rivastigmine are the three acetylcholinesterase inhibitors (AChEIs), out of a total of only four medications prescribed in the treatment of Alzheimer's Disease (AD) and related dementias. These medications are known to be associated with bradycardia given their mechanism of action of increasing acetylcholine (ACh). However, in March 2015, donepezil was added to the CredibleMeds “known‐risk” category, a list where medications have a documented risk for acquired long‐QT syndrome (ALQTS) and torsades de pointes (TdP) – a malignant ventricular arrhythmia that is a different adverse event than bradycardia (and is not necessarily associated with ACh action). The purpose of this article is to review the three AChEIs, especially with regards to mechanistic differences that may explain why only donepezil poses this risk; several pharmacological mechanisms may explain why. However, from an empirical point‐of‐view, aside from some case‐reports, only a limited number of studies have generated relevant information regarding AChEIs' and electrocardiogram findings; none have specifically compared donepezil against galantamine or rivastigmine for malignant arrhythmias such as TdP. Currently, the choice of one of the three AChEIs for treatment of AD symptoms is primarily dependent upon clinician and patient preference. However, clinicians should be aware of the potential increased risk associated with donepezil. There is a need to examine the comparative risk of malignant arrhythmias among AChEIs users in real‐world practice; this may have important implications with regards to changes in AChEI prescribing patterns.

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Cardiovascular pharmacodynamics of donepezil hydrochloride on the PR and QT intervals in patients with dementia

Abstract: Care should be taken when administering donepezil to patients with atrioventricular block, or patients taking other drugs that can prolong the PR interval. Copyright © 2014 John Wiley & Sons, Ltd.

Cited by 18 publications

References 23 publications

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

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

Electrocardiogram Changes of Donepezil Administration in Elderly Patients with Ischemic Heart Disease

Comparative risk of cardiac arrhythmias associated with acetylcholinesterase inhibitors used in treatment of dementias – A narrative review

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