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

摘要 我是约翰霍普金斯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 评估疗养院和其他机构治疗的使用，安全性和有效性 设置.为了实现这一目标，我寻求K 01指导职业发展奖，以获得技能，知识和 通过培训、指导和科学研究积累经验。我的导师团队由G博士领导。Caleb 亚历山大和辛西娅博伊德，包括药物流行病学，因果推理，临床 药理学和老年医学将支持我在（1）先进的方法， 药物流行病学;（2）因果推理的新技术;（3）临床老年病学。四分之一的护士 美国的家庭居民患有房颤，预计房颤的患病率将 到2050年，由于人口老龄化，60多年来，华法林一直是主要的治疗方法 用于降低房颤患者心源性卒中的风险。然而，直接的到来- 作用口服抗凝剂（DOAC），包括直接Xa因子抑制剂（例如，阿哌沙班）和直接 凝血酶抑制剂（例如，达比加群），已经改变了治疗前景。在养老院的居民中 在房颤患者中，近四分之一接受DOAC。虽然涉及DOAC的药物相互作用是 DOAC的数量少于华法林，但它有可能与许多药物相互作用， 通过改变细胞色素P450酶或P-糖蛋白（一种药物）的活性， 传送器疗养院的居民面临着这种药物相互作用的风险增加，因为 生理储备减少、多种用药以及年龄相关的药代动力学和药效学 如肾功能下降等变化。我建议研究药物对临床和卫生系统的影响- 通过（1）确定房颤患者的患病率， 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）量化涉及DOAC的药物相互作用与大出血的相关性， 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。做 因此，我将使用国家疗养院数据，“最小数据集”，以及关联的医疗保险A、B和D部分索赔 数据我的工作将产生关于药物相互作用的新的临床和经济信息， DOAC旨在提高护理质量和护理院的患者结局。此外，我的训练和 通过这个K 01的专业成长将作为一个垫脚石，将促进我作为一个 科学家和公共卫生专家，专门从事老年药物流行病学的重要领域。

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.