Department of Pharmaceutical Health Outcomes and Policy, College of Pharmacy, University of Houston, 4849 Calhoun Road, Houston, TX, 77204-5047, USA.
Department of Pharmacy Practice and Translational Research, College of Pharmacy, University of Houston, Houston, TX, USA.
Drugs Aging. 2021 Jul;38(7):593-602. doi: 10.1007/s40266-021-00863-5. Epub 2021 May 24.
Acetylcholinesterase inhibitors (AChEIs) have been associated with an increased risk of starting antimuscarinic treatment to treat overactive bladder (OAB)-an example of a prescribing cascade. Limited comparative data exist regarding the prescribing cascade of antimuscarinics across individual AChEIs in older adults with dementia.
This study examined the association between individual AChEI use and antimuscarinic cascade in older adults with dementia.
We conducted a new user retrospective cohort study from January 2005 to December 2018 using data from the TriNetX electronic medical record database, a federated electronic medical records network in the US. The cohort included patients 65 years or older with a diagnosis of dementia using AChEIs (donepezil, galantamine, or rivastigmine). Individual AChEIs were identified with index dates from 1 January 2006 to 31 June 2018, with a 1-year washout period. The study excluded patients with any antimuscarinic use and OAB diagnosis 1 year before the AChEI index date. The primary outcome of interest was the prescription of antimuscarinics within 6 months of the AChEI index date. A Cox proportional hazard model was used to assess the association between individual incident AChEI use and antimuscarinic prescribing cascade after controlling for several covariates.
The study included 47,059 older adults with dementia who were incident users of AChEIs. Most of these patients were initiated with donepezil (83.1%), followed by rivastigmine (12.3%) and galantamine (4.6%). Overall, 8.16% of the study cohort had incident OAB diagnosis or antimuscarinic prescription. Antimuscarinics were initiated by 1725 (3.7%) older adults with dementia within 6 months of AChEI prescription, and cascade varied widely across individual agents-donepezil (3.9%), rivastigmine (2.6%), and galantamine (2.9%). Cox proportional hazard analyses revealed that donepezil users had an increased risk of receiving antimuscarinics (adjusted hazard ratio 1.55, 95% confidence interval 1.31-1.83) compared with rivastigmine. The findings were consistent in sensitivity analyses.
This study found that donepezil use is more likely to lead to antimuscarinic cascade than rivastigmine. Future studies are needed to determine the potential consequences of this cascade in dementia.
乙酰胆碱酯酶抑制剂（AChEIs）与开始使用抗毒蕈碱药物治疗过度活跃膀胱（OAB）的风险增加有关 - 这是处方级联的一个例子。在患有痴呆症的老年人中，关于个别 AChEI 的抗毒蕈碱药物的处方级联，现有有限的比较数据。
本研究旨在研究个体 AChEI 使用与痴呆症老年人的抗毒蕈碱药物级联之间的关联。
我们使用来自美国 TriNetX 电子病历数据库的新用户回顾性队列研究数据，进行了一项从 2005 年 1 月至 2018 年 12 月的研究。该队列包括使用 AChEI（多奈哌齐、加兰他敏或利伐斯的明）的年龄在 65 岁或以上的痴呆症患者。个体 AChEI 于 2006 年 1 月 1 日至 2018 年 6 月 31 日期间确定索引日期，有 1 年的洗脱期。研究排除了在 AChEI 索引日期前 1 年有任何抗毒蕈碱药物使用和 OAB 诊断的患者。主要观察结果是在 AChEI 索引日期后 6 个月内开具抗毒蕈碱药物。使用 Cox 比例风险模型评估了个体新发生的 AChEI 使用与抗毒蕈碱药物处方级联之间的关联，同时控制了多个协变量。
研究纳入了 47059 名患有痴呆症的老年人，他们是 AChEI 的新使用者。这些患者中大多数（83.1%）开始使用多奈哌齐，其次是利伐斯的明（12.3%）和加兰他敏（4.6%）。总体而言，研究队列中有 8.16%的患者有新的 OAB 诊断或抗毒蕈碱药物处方。在 AChEI 处方后 6 个月内，有 1725 名（3.7%）痴呆症老年人开始使用抗毒蕈碱药物，并且个别药物的级联差异很大 - 多奈哌齐（3.9%）、利伐斯的明（2.6%）和加兰他敏（2.9%）。Cox 比例风险分析显示，与利伐斯的明相比，多奈哌齐使用者接受抗毒蕈碱药物的风险增加（调整后的危险比 1.55，95%置信区间 1.31-1.83）。敏感性分析结果一致。
本研究发现，与利伐斯的明相比，多奈哌齐的使用更可能导致抗毒蕈碱药物级联。需要进一步的研究来确定这种级联在痴呆症中的潜在后果。
