Cardiovascular Effects of Donepezil in Patients with Dementia

Abstract

Heart rate variability is used to assess cardiovascular autonomic function. The cholinesterase inhibitor donepezil potentially affects parasympathetic activity. Twenty participants with Alzheimer’s disease or dementia with Lewy bodies were treated with donepezil in a pilot study. Power spectral analysis was used to analyse 5 min of beat-to-beat RR interval data in 15 cases. Heart rate variability was significantly reduced following treatment with donepezil; mainly for high frequency (median changed from 581 to 78 ms²; p = 0.001) but also for total power (median changed from 1,563 to 844 ms²; p = 0.047). Donepezil may adversely influence cardiovascular autonomic control. These results indicate the need for larger controlled trials to further investigate the cardiovascular effects of donepezil.

Lower Barthel Index Scores Predict Less Prescription of Pharmacological Therapy in Elderly Patients with Alzheimer Disease

“…One study showed that heart rate variability, which is used to assess autonomic function, is impaired by donepezil in people with neurodegenerative dementia. It also revealed a tendency for hypotensive disorders to be exaggerated [27] . It is known that acetylcholine affects blood pressure and the heart rate by both central and peripheral means.…”

“…The cardiovascular effects of AChEI are complex, but they generally augment vagal influences on the heart and can theoretically induce sinus bradycardia or sinoatrial block, and aggravate preexisting sinus node disease and atrioventricular block promoting bradycardia [26,27] . In this way, patients with heart failure frequently receive treatment with ␤ -blockers and on occasion may have bradycardia, which might explain the trend to significance observed in the univariate analysis.…”

Donepezil: A Review of Pharmacological Characteristics and Role in the Management of Alzheimer Disease

“…58 Another study showed no changes in heart rate variation. 59,60 Several cases of syncope have been reported in patients who have been receiving donepezil treatment 50,57 ; 69% of these cases of syncope were associated with carotid sinus syndrome, sinus node dysfunction, complete atrioventricular block, paroxysmal atrial fibrillation, and severe orthostatic hypotension, whereas in 31% of the cases no cause of syncope was found.…”

“…59,60 Several cases of syncope have been reported in patients who have been receiving donepezil treatment 50,57 ; 69% of these cases of syncope were associated with carotid sinus syndrome, sinus node dysfunction, complete atrioventricular block, paroxysmal atrial fibrillation, and severe orthostatic hypotension, whereas in 31% of the cases no cause of syncope was found. 57 Isik et al 61 performed an openlabel study involving 52 AD patients, a much larger study population as compared with previous works, [58][59][60] and found no changes in electrocardiogram or blood pressure, and concluded that the previous studies were confounded by comorbidities and medications. However, there is no clear evidence of the effect of donepezil on the cardiovascular autonomic system, and further randomized double-blind controlled studies are needed to assess the full extent of this effect.…”

Cardiale neveneffecten van cholinesteraseremmers: een reden tot terughoudendheid in voorschrijven?

“…[7][8][9] Studies met het niet in Nederland verkrijgbare donepezil lieten zien dat de verhoogde parasympatische activiteit leidde tot afname van de hartslag-variabiliteit (HRV). 10 De aanwezigheid van enige HRV is een teken van cardiovasculaire gezondheid en afname hiervan geeft aan dat er sprake is van een slechte autonome homeostatische controle.…”