This NIH post-doctoral fellowship (F32) application is designed to promote the training of Dr. Magdalene Assimon, PharmD, MS, post-doctoral fellow and concurrent Epidemiology PhD student at the University of North Carolina, and to provide her with a foundation for an independent research career. The Candidate is a trained nephrology pharmacist with experience in clinical research. Her goal is to integrate these skills with focused training in pharmacoepidemiology to become an independent scientist who conducts dialysis outcomes research focused on drug safety and effectiveness. During the F32 training period, the Candidate will complete her PhD degree under the mentorship of her sponsor Dr. M. Alan Brookhart, PhD, Professor of Epidemiology. In addition, collaborative clinical mentorship will be provided by Dr. Jennifer Flythe, MD, MPH, Assistant Professor of Medicine. The proposed project is a retrospective cohort study assessing the comparative effectiveness of beta adrenergic blocker therapy in a cohort of 21,000 prevalent hemodialysis (HD) patients using the clinically rich research database of a large United States dialysis provider linked with the United States Renal Data System. Cardiovascular disease remains the leading cause of morbidity and mortality among HD patients, accounting for 30% hospitalizations and 50% of deaths annually. In the general population, pharmaceutical interventions such as beta blockers improve clinical outcomes in heart failure, atrial fibrillation and post-myocardial infarction. The cardioprotective benefit of beta blocker therapy has not been evaluated by large-scale clinical trials in HD patients, a population with unique drug dosing considerations. Pharmacokinetic and pharmacologic differences across beta blocker subclasses may alter drug efficacy and safety profiles in these individuals. Despite the evidence void, over 60% of HD patients receive beta blockers. A clear understanding of the longitudinal patterns of beta blocker use in the real-world setting combined with a rigorous assessment of the comparative effectiveness of beta blocker subclasses is urgently needed to improve clinical decision making. Using modern study designs and innovative statistical methods, this proposal aims to: 1) examine long-term beta blocker utilization patterns in the HD population, and 2) assess the comparative mortality and hospitalization risks of cardioselective beta blocker versus alpha-beta blocker therapy among HD patients. The proposed work has high potential to make a significant impact. Completion of the study aims will advance our understanding of the beta blocker subtype that may offer superior clinical benefits to HD patients, and will provide data to guide the design of future randomized trials. The proposed work is realistic and feasible within the award period. Importantly, the proposed research and multifaceted career development activities will foster Dr. Assimon's growth as an independent clinical investigator by allowing her to develop new research skills, create collaborative research networks and generate preliminary data which will serve as the foundation for a future career development award application.
In the general population, beta blockers reduce hospitalizations and mortality among patients with heart failure, atrial fibrillation and after a hart attack. Despite the widespread use of these medications by hemodialysis patients, a population with unique drug dosing and administration considerations, the efficacy of beta blocker subtypes has not been extensively evaluated in end-stage kidney disease. The current proposal aims to shed light on this important topic by assessing the comparative effectiveness of beta blocker subclasses in the hemodialysis population.
