Drug-Drug Interactions Involving Direct-Acting Oral Anticoagulants in Nursing Home Residents

疗养院居民中涉及直接作用口服抗凝剂的药物相互作用

基本信息

批准号：
10399514
负责人：
Hemalkumar B. Mehta
金额：
$ 12.94万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10399514
关键词：
ABCB1 gene Affect Aging Anticoagulants Antiepileptic Agents Antithrombin III Atrial Fibrillation Blood CYP3A4 gene Clinical Clinical Pharmacology Crossover Design Cytochrome P450 Data Data Set Development Drug Interactions Drug Kinetics Drug usage Economics Elderly Electronic Health Record Elements Enzymes Epidemiology Exposure to Fostering Foundations Geriatrics Goals Growth Health system Hemorrhage Home Nursing Care Hospitalization K-Series Research Career Programs Knowledge Legal patent Link Logistic Regressions Long-Term Care Nursing Lovastatin Medicare Medicare Part A Mentored Research Scientist Development Award Mentors Mentorship Metabolism Methods Modeling Monitor Nursing Homes Oral Outcome Pathway interactions Patient-Focused Outcomes Patients Persons Pharmaceutical Preparations Pharmacoepidemiology Physicians Physiological Policies Polypharmacy Population Prevalence Probability Provider Public Health Public Health Schools Quality of Care Renal function Research Research Project Grants Risk Safety Scientist Series Simvastatin Stratification Stroke System Techniques Thrombin Time Training United States Verapamil Vulnerable Populations Warfarin Weight Work adverse outcome age related care outcomes career clinically significant computerized cost experience expiration improved improved outcome inhibitor novel pharmacokinetics and pharmacodynamics point of care professor skill acquisition skills stroke risk therapeutic effectiveness thromboembolic stroke tool

项目摘要

ABSTRACT I am an Assistant Professor of Epidemiology at the Johns Hopkins Bloomberg School of Public Health. My career goal is to become a leader in the field of geriatric pharmacoepidemiology, with a particular emphasis on rigorous assessments of the use, safety and effectiveness of therapeutics in nursing homes and other institutional settings. To achieve this goal, I seek a K01 Mentored Career Development Award to gain skills, knowledge and experience through training, mentorship and scientific research. My mentorship team, led by Dr. G. Caleb Alexander and Cynthia Boyd and including experts in pharmacoepidemiology, causal inference, clinical pharmacology and geriatric medicine will support my training in (1) advanced methods in pharmacoepidemiology; (2) novel techniques in causal inference; and (3) clinical geriatrics. One in four nursing home residents in the United States has atrial fibrillation and the prevalence of atrial fibrillation is projected to double by 2050 due to the aging of the population. For more than 60 years, warfarin has been the main treatment used to reduce the risk of cardioembolic stroke in patients with atrial fibrillation. However, the advent of direct- acting oral anticoagulants (DOACs), including both direct Factor Xa inhibitors (e.g., apixaban) and direct thrombin inhibitors (e.g., dabigatran), has transformed the treatment landscape. Among nursing home residents with atrial fibrillation, nearly one-fourth receive DOACs. Although drug-drug interactions involving DOACs are less numerous than those with warfarin, DOACs have the potential to interact with many drugs that influence their pharmacokinetics through alterations in cytochrome P450 enzymes or the activity of P-glycoprotein, a drug transporter. Nursing home residents are at increased risk of such drug-drug interactions because of the decreased physiologic reserve, polypharmacy, and age-related pharmacokinetic and pharmacodynamic changes such as decreased renal function. I propose to examine the clinical and health system impact of drug- drug interactions from DOACs in nursing home residents with atrial fibrillation by (1) determining the prevalence of drug-drug interactions involving DOACs, and patient, provider and nursing home factors associated with their occurrences; (2) quantifying the association of drug-drug interactions involving DOACs with major bleeding and stroke; and (3) evaluating the association of drug-drug interactions involving DOACs with Medicare costs. To do so, I will use national nursing home data, the “Minimum Data Set,” and linked Medicare Parts A, B and D claims data. My work will generate novel clinical and economic information regarding drug-drug interactions involving DOACs to improve the quality of care and patient outcomes in nursing homes. In addition, my training and professional growth through this K01 will serve as a stepping-stone that will foster my further development as a scientist and public health expert specializing in the important field of geriatric pharmacoepidemiology.

抽象的我是约翰霍普金斯大学彭博公共卫生学院的流行病学助理教授我的职业生涯。目标是成为老年药物流行病学领域的领导者，特别强调严格的评估疗养院和其他机构治疗方法的使用、安全性和有效性为了实现这一目标，我寻求 K01 指导职业发展奖来获得技能、知识和知识。我的导师团队由 G. Caleb 博士领导，通过培训、指导和科学研究获得经验。亚历山大·博伊德 (Alexander Boyd) 和辛西娅·博伊德 (Cynthia Boyd) 以及药物流行病学、因果推断、临床药理学和老年医学将支持我在（1）先进方法方面的培训药物流行病学；（2）因果推理新技术；（3）临床老年病学。美国的家庭居民患有心房颤动，并且心房颤动的患病率预计将由于人口老龄化，到 2050 年这一数字将翻一番 60 多年来，华法林一直是主要的治疗方法。用于降低心房颤动患者发生心源性卒中的风险。口服抗凝药 (DOAC)，包括直接 Xa 因子抑制剂（例如阿哌沙班）和直接 Xa 因子抑制剂（例如阿哌沙班）凝血酶抑制剂（例如达比加群）改变了疗养院居民的治疗格局。患有心房颤动的患者中，近四分之一接受 DOAC，尽管涉及 DOAC 的药物间相互作用是存在的。 DOAC 的数量比华法林的数量要少，但它有可能与许多影响药物相互作用的药物相互作用。通过改变细胞色素 P450 酶或 P-糖蛋白（一种药物）的活性来改变其药代动力学由于转运者，疗养院居民发生此类药物相互作用的风险增加。生理储备减少、多重用药以及与年龄相关的药代动力学和药效学我建议检查药物对临床和健康系统的影响。通过 (1) 确定患病率来评估患有心房颤动的疗养院居民中 DOAC 的药物相互作用涉及 DOAC 的药物相互作用，以及与其相关的患者、提供者和疗养院因素 (2) 量化药物间相互作用 DOAC 与大出血的关联并涉及中风；(3) 评估涉及 DOAC 的药物相互作用与医疗保险费用的关联。因此，我将使用国家疗养院数据、“最小数据集”以及链接的 Medicare A、B 和 D 部分索赔我的工作将产生有关药物相互作用的新颖的临床和经济信息。 DOAC 旨在提高疗养院的护理质量和患者治疗效果。通过 K01 获得的专业成长将成为促进我进一步发展的垫脚石专门研究老年药物流行病学重要领域的科学家和公共卫生专家。