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

摘要 我是约翰霍普金斯大学布隆伯格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 疗养院和其他机构中治疗药物的使用、安全性和有效性的评估 设置。为了实现这一目标，我寻求K01导师职业发展奖，以获得技能、知识和 通过培训、指导和科学研究获得经验。我的导师团队，由G.Caleb博士领导 Alexander和Cynthia Boyd，包括药物流行病学、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)因果推断的新技术；(3)临床老年病学。每四个护士中就有一个 美国家庭居民患有房颤，预计房颤的患病率将 由于人口老龄化，到2050年将翻一番。60多年来，华法林一直是主要的治疗方法 用于降低房颤患者发生心源性中风的风险。然而，直接- 有效的口服抗凝剂(DOAC)，包括直接凝血因子Xa抑制剂(如阿匹沙班)和直接抗凝剂 凝血酶抑制剂(如达比加特兰)改变了治疗格局。在疗养院居民中 对于房颤，近四分之一的人接受DOAC。尽管涉及DOAC的药物-药物相互作用 与使用华法林的药物相比，DOAC的数量较少，因此可能与许多影响 通过细胞色素P450酶的变化或药物P-糖蛋白的活性来研究它们的药代动力学 传送器。疗养院居民发生这种药物-药物相互作用的风险增加，因为 生理储备减少、多药联用以及与年龄相关的药代动力学和药效学 肾功能下降等变化。我建议研究药物对临床和卫生系统的影响- 疗养院房颤患者中DOAC的药物相互作用：(1)确定患病率 涉及DOAC的药物-药物相互作用，以及与其相关的患者、提供者和疗养院因素 发生；(2)量化涉及DOAC的药物-药物相互作用与大出血和 以及(3)评估涉及DOAC的药物-药物相互作用与医疗保险成本的关联。去做 因此，我将使用国家疗养院数据、“最低数据集”以及相关联的联邦医疗保险A、B和D部分索赔 数据。我的工作将产生有关药物-药物相互作用的新的临床和经济信息，包括 DOAC，以改善疗养院的护理质量和患者结局。另外，我的训练和 通过K01的职业成长将成为我作为一名 专攻老年药物流行病学重要领域的科学家和公共卫生专家。

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.