Project Summary/Abstract This is a Beeson (K76) career development award for Sachin J Shah, MD, MPH, a physician-investigator trained in internal medicine, clinical epidemiology, and aging research. Dr. Shah is an Assistant Professor in the Division of Hospital Medicine at the University of California, San Francisco. Dr. Shah's long-term goal is to build evidence to individualize treatment recommendations for older adults facing high-risk, high-benefit therapeutic decisions using new epidemiologic methods and geriatric research principles. The decision to use anticoagulants in older adults with atrial fibrillation (AF) is the paradigm of a high-stakes therapeutic decision because while anticoagulants prevent stroke, they increase the risk of bleeding complications. Guidelines use a one-size-fits-all approach; for older adults, they recommend near-universal anticoagulant use. In numerous studies of clinical practice, physicians report concern with the current approach voicing the need to individualize treatment recommendations for older adults. This proposal addresses the pressing need to individualize anticoagulant treatment decisions in older adults with AF through two aims. Aim 1: Develop and validate individualized estimates of the treatment effect of anticoagulants for ischemic stroke prevention in older adults with AF. This aim will use clinical trial and observational data to develop and validate a treatment effect model that will estimate individual-level treatment benefit. Aim 2: Ascertain functional outcomes after major extracranial hemorrhage, both short-term and longer-term. The functional outcomes following major hemorrhage, a key adverse event of anticoagulant therapy, are unclear, especially in older adults. Through two studies, this proposal will determine the short- and long-term functional outcomes following major hemorrhage. Dr. Shah's exceptional, multidisciplinary mentoring team is led by Dr. Margaret Fang, nationally recognized for her work studying the clinical outcomes of anticoagulants in older adults and co-mentored by Dr. Kenneth Covinsky, whose nationally recognized research program has advanced our understanding of the predictors and outcomes of disability in older adults. This career development award will support Dr. Shah's transition to research independence through mentorship and focused training in (1) measuring heterogeneous treatment effects using novel epidemiologic tools, (2) primary data collection to build prospective cohorts of older adults, (3) designing decision aids and (4) leadership development to lead cross-disciplinary, multi-institutional research teams. This proposal will support a development grant to design and pilot a clinical decision tool for older adults considering anticoagulant and a project grant to measure heterogeneous treatment effects of procedural interventions in older adults with AF. The proposed research and training aims will provide Dr. Shah with the data, training, and experience to support competitive R-series applications.

Project Narrative Atrial fibrillation is the most common heart rhythm disorder in older adults, and it substantially increases the risk of disabling strokes. Anticoagulant treatment reduces the risk of stroke but increases the likelihood of disabling bleeding events. We lack a way to individualize treatment decisions for older adults—this proposal will use multiple studies to better define the individual risk and benefits of anticoagulants in older adults with atrial fibrillation.