Masurkar Prajakta P, Chatterjee Satabdi, Sherer Jeffrey T, Chen Hua, Johnson Michael L, Aparasu Rajender R
Department of Pharmaceutical Health Outcomes and Policy, College of Pharmacy, University of Houston, 4849 Calhoun Road, Houston, TX, 77204-5047, USA.
Boehringer-Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA.
Drugs Aging. 2022 Jun;39(6):453-465. doi: 10.1007/s40266-022-00944-z. Epub 2022 Jun 6.
Cholinesterase inhibitors (ChEIs) are used as first-line pharmacotherapy to manage dementia. However, there are limited data regarding their relative safety. This study evaluated the risk of serious adverse events (SAEs) associated with individual ChEIs in older adults with dementia and also examined sex-based and dose-based effects on this risk.
This was a retrospective cohort study using 2013-2015 US Medicare claims data involving Parts A, B, and D. Patients aged ≥ 65 years with a dementia diagnosis and incident use of the ChEIs, namely donepezil, galantamine, or rivastigmine, were included. The primary outcome of interest was SAEs defined as emergency department visits, inpatient hospitalizations, or death within 6 months of ChEI initiation. Multivariable Cox proportional hazards regression with propensity score (PS) as a covariate and inverse probability of treatment weighting generated using generalized boosted models was used to assess the risk of SAEs across individual ChEIs.
The study included 767,684 older adults with dementia who were incident new users of ChEIs (donepezil 79.42%, rivastigmine 17.67%, galantamine 2.91%). SAEs were observed in 15.5% of the cohort within 6 months of ChEI prescription. Cox regression model with PS as covariate found that patients prescribed rivastigmine (adjusted hazard ratio [aHR] 1.12; 95% CI 1.03-1.33) and galantamine (aHR 1.51; 95% CI 1.24-1.84) were at increased risk of SAEs compared with patients on donepezil. Stratified analyses revealed that rivastigmine was associated with an 18% increased risk for SAEs in females (aHR 1.18; 95% CI 1.06-1.31), and galantamine was associated with a 71% increased risk in males (aHR 1.71; 95% CI 1.17-2.51) compared with donepezil. High and recommended index doses of rivastigmine and galantamine were associated with an increased risk of SAEs compared with donepezil. The findings were consistent in sensitivity analyses.
The study found that the risk of SAEs varied across individual ChEIs, with sex and dose moderating these effects. Therefore, these moderating effects should be carefully considered in personalizing dementia care.
胆碱酯酶抑制剂（ChEIs）被用作治疗痴呆症的一线药物疗法。然而，关于其相对安全性的数据有限。本研究评估了痴呆症老年患者中与个体ChEIs相关的严重不良事件（SAEs）风险，并探讨了性别和剂量对该风险的影响。
这是一项回顾性队列研究，使用了2013 - 2015年美国医疗保险A、B和D部分的理赔数据。纳入年龄≥65岁、诊断为痴呆症且首次使用ChEIs（即多奈哌齐、加兰他敏或卡巴拉汀）的患者。主要关注的结局是SAEs，定义为在开始使用ChEIs后6个月内的急诊就诊、住院治疗或死亡。使用倾向评分（PS）作为协变量的多变量Cox比例风险回归以及使用广义增强模型生成的治疗加权逆概率，来评估个体ChEIs发生SAEs的风险。
该研究纳入了767,684名痴呆症老年患者，他们是ChEIs的首次使用者（多奈哌齐79.42%，卡巴拉汀17.67%，加兰他敏2.91%）。在ChEIs处方后6个月内，该队列中有15.5%的患者发生了SAEs。以PS作为协变量的Cox回归模型发现，与使用多奈哌齐的患者相比，使用卡巴拉汀（调整后风险比[aHR] 1.12；95%置信区间[CI] 1.03 - 1.33）和加兰他敏（aHR 1.51；95% CI 1.24 - 1.84）的患者发生SAEs的风险增加。分层分析显示，与多奈哌齐相比，卡巴拉汀使女性发生SAEs的风险增加18%（aHR 1.18；95% CI 1.06 - 1.31），加兰他敏使男性发生SAEs的风险增加71%（aHR 1.71；95% CI 1.17 - 2.51）。与多奈哌齐相比，卡巴拉汀和加兰他敏的高剂量和推荐指标剂量与SAEs风险增加相关。敏感性分析的结果一致。
该研究发现，不同个体ChEIs发生SAEs的风险各不相同，性别和剂量会影响这些风险。因此，在痴呆症护理个性化过程中应仔细考虑这些影响因素。
