Effect of QT Prolongation in Patients Taking Cholinesterase Inhibitors (Donepezil) for Alzheimer’s Disease

Background: Cholinesterase inhibitors such as donepezil are used in the treatment of Alzheimer’s disease. Patients taking cholinesterase inhibitors can develop cholinergically mediated QT prolongation, which may lead to life-threatening arrhythmias. In this study we investigated the corrected QT interval (QTc) of patients taking donepezil. Methods and Results: This study enrolled 114 outpatients attending Tarumizu Chuo Hospital. Subjects were divided into a donepezil group (n=57) or an age- and sex-matched control group (n=57). Physical findings, laboratory data, and electrocardiographic parameters were compared between the groups. QTc was significantly prolonged (mean [±SD] 0.443±0.032 s vs. 0.426±0.026s; P<0.001) and the percentage of patients with prolonged QTc was significantly higher (30% vs. 9%; P<0.01) in the donepezil than control group. Furthermore, in the donepezil group, QTc was significantly prolonged after patients started taking donepezil compared with baseline (from 0.433±0.034 to 0.442±0.033s; n=46; P<0.05). On univariate analysis, QTc was significantly associated with taking donepezil, as well as with hemoglobin, serum calcium concentration, and estimated glomerular filtration rate (eGFR; all P<0.01). On multivariate analysis, QTc was significantly associated with taking donepezil (P<0.001), serum potassium concentration (P<0.05), and eGFR (P<0.05). Conclusions: The incidence of QTc prolongation was more frequent in patients taking donepezil than in the control group, and was difficult to predict. Periodic electrocardiogram examinations are recommended considering the possibility of adverse events, such as fatal arrhythmias.