Malone Katie, Hancox Jules C
School of Physiology, Pharmacology and Neuroscience, University of Bristol, University Walk, Bristol, UK.
School of Physiology, Pharmacology and Neuroscience, University of Bristol, University Walk, Biomedical Sciences Building, Bristol, BS8 1TD, UK.
Ther Adv Drug Saf. 2020 Aug 17;11:2042098620942416. doi: 10.1177/2042098620942416. eCollection 2020.
Acetylcholinesterase inhibitors (AChEis) including donepezil, galantamine and rivastigmine are used to treat Alzheimer's disease (AD). This study aimed to evaluate evidence from the case report literature for an association between these agents and risk of QT interval prolongation and (TdP) arrhythmia.
Published literature was mined with predetermined MeSH terms for each of donepezil, galantamine and rivastigmine, to identify cases of QT interval prolongation and TdP. Case reports were analysed using causality scales and a QT interval nomogram.
A total of 13 case reports were found (10 for donepezil, 2 for galantamine and 1 for rivastigmine) with rate corrected QT interval (QT) prolongation. Five cases with donepezil exhibited TdP. TdP was not reported in the cases with galantamine and rivastigmine. The use of a QT heart rate nomogram highlighted risk with donepezil compared with the other two drugs and the application of the Naranjo causality scale suggested probable or possible causation for all donepezil cases. All patients had at least two other risk factors for TdP, including modifiable risk factors such as electrolyte disturbances, bradycardia, co-administration of QT prolonging drugs. A number of recent cases involved recent changes in medication.
Our evaluation of the case report literature suggests that there is evidence for a causal association between donepezil and QT/TdP risk. Attention to risk factors for QT prolongation/TdP should be exercised when prescribing donepezil and modifiable risk factors corrected. Owing to the low number of cases with galantamine and rivastigmine, further work is needed to establish whether these drugs may be more suitable than donepezil for patients with other risk factors for TdP.
包括多奈哌齐、加兰他敏和卡巴拉汀在内的乙酰胆碱酯酶抑制剂用于治疗阿尔茨海默病（AD）。本研究旨在评估病例报告文献中关于这些药物与QT间期延长及尖端扭转型室性心动过速（TdP）心律失常风险之间关联的证据。
使用针对多奈哌齐、加兰他敏和卡巴拉汀各自预先确定的医学主题词（MeSH）对已发表文献进行检索，以识别QT间期延长和TdP的病例。使用因果关系量表和QT间期列线图对病例报告进行分析。
共发现13例病例报告（多奈哌齐10例、加兰他敏2例、卡巴拉汀1例）存在心率校正QT间期（QT）延长。多奈哌齐治疗的5例出现了TdP。加兰他敏和卡巴拉汀治疗的病例未报告TdP。与其他两种药物相比，QT心率列线图显示多奈哌齐存在风险，应用纳伦霍因果关系量表表明所有多奈哌齐病例可能或很可能存在因果关系。所有患者至少还有另外两个TdP风险因素，包括可改变的风险因素，如电解质紊乱、心动过缓、联用延长QT间期的药物。近期的一些病例涉及近期用药变化。
我们对病例报告文献的评估表明，有证据支持多奈哌齐与QT/TdP风险之间存在因果关联。开具多奈哌齐处方时应关注QT延长/TdP的风险因素并纠正可改变的风险因素。由于加兰他敏和卡巴拉汀的病例数较少，需要进一步研究以确定对于有其他TdP风险因素的患者，这些药物是否比多奈哌齐更合适。
