Cardiac Safety of Donepezil in Elderly Patients with Alzheimer Disease

Abstract

Objective Donepezil is a widely used cholinesterase inhibitor for the treatment of Alzheimer's disease (AD), however its cholinergic adverse side effects on the cardiovascular system are still unclear. In this study, we aimed to examine the adverse side effects caused by donepezil on cardiac rhythm and postural blood pressure changes in elderly patients with Alzheimer Disease. Methods The ECG parameters including heart rate, PR, QT, QTc interval and QRS duration and postural blood pressure changes were recorded at the baseline and at each donepezil dose level (5 and 10 mg/d). Patients Seventy-one consecutive patients who were referred by primary care centers to a Geriatric Clinic were enrolled and underwent comprehensive geriatric assessment. Results Fifty-two subjects completed the study. There were no significant changes relative to the baseline in any of the ECG parameters or arterial blood pressure at any of the investigated dosages of donepezil. Conclusion It was demonstrated that donepezil was not associated with increased negative chronotropic, arrhythmogenic or hypotensive effects for elderly patients with Alzheimer's disease.

Nicotinic Receptors in Neurodegeneration

“…It has also been described that acetylcholinesterase inhibitors may also induce cardiovascular side-effects although their effects on the cardiovascular system are still unclear. In this regard, it has been recently described that Donepezil, galantamine and rivastigmine are not associated with cardiovascular toxicity in elderly patients with AD [118]. …”

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

“…Isik et al . directly compared the PR interval in a prospective study of 71 patients with Alzheimer's disease and reported no impact of donepezil hydrochloride on either heart rate or PR interval (Isik et al ., ). The study by Isik et al .…”

“…To date, various reports have been made of cases of atrioventricular block caused by donepezil hydrochloride (Suleyman et al ., ; Tanaka et al ., ), and we have also reported a case in which the administration of donepezil hydrochloride resulted in prolonged PR interval, and the additional administration of memantine further worsened the prolonged PR interval (Igeta et al ., ). Some reports, however, have suggested no clear prolongation of PR interval as a result of the administration of donepezil hydrochloride (Feldman et al ., ; Tariot et al ., ; Winblad et al ., ; Black et al ., ; Froelich et al ., ; Isik et al ., ), resulting in conflicting observations. Therefore, we implemented a study of the impact of donepezil hydrochloride administration on RR, PR, and QT intervals.…”

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

“…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.…”