Patient Oriented Research in Anticoagulation

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DESCRIPTION (provided by applicant): Stephen E. Kimmel, MD, MSCE is currently an Assistant Professor of Medicine in the Division of Cardiology, and Assistant Professor of Epidemiology in the Department of Biostatistics and Epidemiology, and a Senior Scholar (core faculty member) in the Center for Clinical Epidemiology and Biostatistics (CCEB) at the University of Pennsylvania (Penn). He is an established clinical researcher with an extensive track record of successful research. His research record attests to his commitment to a career in patient-oriented research, which has been focused on the effects of medications and devices on cardiovascular outcomes, and his desire to be a mentor. He has applied a wide variety of epidemiologic tools and patient-oriented research methods to address research issues. His immediate and long-term career goals center on his desire and intent to continue to evolve and mature as a patient-oriented researcher, teacher, and mentor. The University of Pennsylvania has committed itself to the development of a strong environment for clinical and patient-oriented research. The resources available to the candidate on the Penn campus include all of the components necessary for successful patient-oriented research and mentoring, including biostatistical support, data management support, and state of the art research/clinical laboratory services. The proposed patient-oriented, NHLBI-funded research project is in its first year. Thromboembolism (TE) can occur in the venous or arterial system and is associated with substantial morbidity and mortality in a large proportion of the population. Although, most of these thromboembolic events can be prevented using warfarin sodium, proper levels of anticoagulation (AC) with warfarin are very difficult to maintain. The reason for the marked intra-patient and inter-patient variability in response to warfarin often remains unknown. The objective of this prospective cohort study is to determine the effects of recently discovered genetic variants (of the CYP2C9 enzyme and apolipoprotein E) and of adherence on AC control. By understanding the effects of genetic polymorphisms; and adherence on AC control via the merger of the disciplines of pharmacogenetics and pharmacoepidemiology, this study hopes to provide critical information to apply clinically (patient pre-screening) and scientifically (development and application of specific strategies targeted at specific patient groups based on the cause of their poor AC control). The ultimate goal is to improve the use of a highly efficacious, but underused, drug, and reduce morbidity and mortality in the large proportion of the population at risk for TE.