Friday, May 9, 2025
5/9/2025
Drug-Drug Interactions Involving Direct-Acting Oral Anticoagulants in Nursing Home Residents - 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.
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