Impact of Prescribing Cascade and Associated Drug Interaction in Alzheimer's Disease

级联处方和相关药物相互作用对阿尔茨海默病的影响

• 批准号: 10212709
• 负责人: Rajender R Aparasu
• 金额: $ 44.99万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10212709
• 关键词: Accounting; Acetylcholine; Acetylcholinesterase; Adverse effects; Adverse event; Age; Alzheimer' s Disease; Alzheimer' s disease patient; American; Anti-Cholinergics; Antipsychotic Agents; Behavioral Model; Behavioral Symptoms; Brain; Cause of Death; Cessation of life; Cholinesterase Inhibitors; Chronic Disease; Clinical; Cognition; Cognitive; Communities; Cox Proportional Hazards Models; Data; Dementia; Drug Interactions; Elderly; Emergency department visit; Enzymes; Expenditure; Galantamine; Goals; Healthcare; Hospitalization; Institutionalization; Lead; Medical; Medicare; Medicare claim; Memantine; Memory impairment; Methods; Neurobehavioral Manifestations; Neurotransmitters; Patients; Pharmaceutical Preparations; Pharmacotherapy; Population; Prevalence; Problem behavior; Prosencephalon; Public Health; Quality of life; Research; Risk; Safety; Sampling; Selection Bias; Serious Adverse Event; Specificity; Testing; Therapeutic; Therapeutic Effect; Treatment Effectiveness; Urinary Incontinence; Variant; aged; base; care costs; cholinergic; cholinergic neuron; cohort; design; donepezil; evidence base; functional decline; hazard; human old age (65+); improved; mortality; neurotransmission; policy implication; prevent; rivastigmine; systematic review

PROJECT SUMMARY/ABSTRACT Dementia is a major public health concern in older adults. Alzheimer’s disease (AD) accounts for 50% to 60% of dementia cases and nearly half of dementia-related deaths. Cholinesterase inhibitors (ChEIs) form the first line of pharmacotherapy for AD. However, the treatment effectiveness of ChEIs is considered modest and their use leads to adverse effects. Urinary incontinence is a prominent adverse effect of ChEI treatment, which is commonly implicated in prescribing cascade - a clinical phenomenon where the ChEI-induced urinary incontinence leads to prescribing of antimuscarinics. ChEIs and antimuscarinics interaction tends to nullify the modest treatment benefit of ChEIs and can worsen AD due to the therapeutically opposing mechanism of actions. This worsening of AD can precipitate additional cascades - prescribing of memantine for moderate-to- severe AD, and/or antipsychotics to manage behavioral symptoms of AD, and/or may lead to Serious Adverse Events (SAEs). Our preliminary analyses revealed that 6% of AD patients initiated antimuscarinics after ChEIs initiation, and memantine and antipsychotics were initiated by 30% and 23% AD patients, respectively, after the initial cascade. Although some studies have described the initial prescribing cascade of ChEIs in AD, none of the studies have evaluated the impact of prescribing cascades due to the drug-drug interaction of ChEIs and antimuscarinics. Therefore, the overall goal of this research is to evaluate the healthcare impact of the prescribing cascades of ChEIs and their associated interactions among community-dwelling older adults with AD. The specific aims of the proposed research are to: (1) examine the extent of prescribing cascades of ChEIs in older adults with AD; and (2) assess all-cause SAEs associated with ChEI-antimuscarinic interaction in older adults with AD. The study will involve propensity score-matched cohort design based on a national cohort of older adults > 65 years with AD. The initial prescribing cascade of ChEIs will include initiation of antimuscarinics. Further cascades will include initiation of memantine (for moderate-to-severe AD) and antipsychotics (for behavioral symptoms of AD). All-cause SAEs s will include all-cause hospitalization, emergency department visits, institutionalization, and mortality. Multi-year multistate Medicare data involving Parts A, B, and D will be used to test the following hypotheses: (i) ChEI-antimuscarinic drug-drug interaction leads to further cascades due to worsening of AD leading to prescribing of memantine for moderate-to-severe AD, as well as prescription of antipsychotics to manage behavioral symptoms of AD, and (ii) there is a greater risk for all-cause SAEs due to ChEI-antimuscarinic interaction. Concomitant ChEI-antimuscarinic users will be compared with concomitant users of ChEIs and mirabegron, a non-anticholinergic alternative. The study will adjust for selection bias within the multivariable context of Anderson Behavioral Model. Robust Cox proportional hazards models will be used to account for the matched sets. The proposed study will have significant clinical and policy implications for preventing, detecting, and reversing prescribing cascades in AD.

项目摘要/摘要 痴呆症是老年人的主要公共卫生问题。阿尔茨海默氏病（AD）占50％至60％ 痴呆病例和几乎一半与痴呆有关的死亡。胆碱酯酶抑制剂（CHEIS）形成第一行 AD药物疗法。但是，Cheis的治疗效果被认为是适度的，它们的使用 导致不利影响。尿失禁是CHEI治疗的显着不利影响， 通常与开处方级联有关 - 一种临床现象，其中chei诱导的尿液 尿失禁会导致抗刺激药的处方。 CHEIS和ANTIMCARICICS互动往往会使该互动无效 由于治疗性相反的机制 动作。广告的这种担心会引起其他级联 - 为现代至现代的纪念品开处方 严重的AD和/或抗精神病药以管理AD的行为症状和/或可能导致严重的不利 事件（SAE）。我们的初步分析表明，有6％的AD患者在CHEIS之后开始抗胰岛素药 启动，美金刚和抗精神病药分别由30％和23％的AD患者启动 最初的级联。尽管一些研究描述了AD中的初始处方Cheis的处方级联 研究评估了由于CHEIS和 抗司法机构。因此，这项研究的总体目标是评估 开处方级联的Cheis及其在社区居住的老年人中的相关互动与 广告。拟议研究的具体目的是：（1）检查开处方级联的程度 AD老年人的Cheis； （2）评估与Chei antimuscarinic相关的全因SAE 老年人与AD的相互作用。该研究将涉及基于A的改进得分匹配的队列设计 全国老年人队列> 65岁。 CHEI的最初处方级联将包括主动性 抗胰岛。进一步的级联将包括纪念倡议（用于现代至重度广告）和 抗精神病药（用于AD的行为症状）。全因SAE将包括全因住院， 急诊室就诊，制度化和死亡率。多年多年医疗保险数据涉及 A部分A，B和D将用于测试以下假设：（i）Chei-antimuscarinic药物互动的相互作用 由于担心广告会导致纪念梅兰丁的处方，导致进一步的级联 AD，以及抗精神病药的处方以管理AD的行为症状，（ii）有更大的 由于Chei antimuscarinic的相互作用而导致全因SAE的风险。伴随的chei antimuscarinic用户将 与Cheis和Mirabegron伴随的使用者相比，它是一种非抗胆碱能替代方案。研究将 在安德森行为模型的多变量上下文中调整选择偏差。强大的考克斯比例 危害模型将用于说明匹配的集合。拟议的研究将具有明显的临床 以及预防，检测和逆转广告中的级联的政策影响。