Nita Limdi, Pharm.D, PhD has built a successful research program focused on antithrombotic therapy pharmacogenomics encompassing both observational and clinical trial designs. Her scientific career goals are to comprehensively understand the clinical, environmental and genetic factors that influence variability in antithrombotic response and to use this information to personalize antithrombotic treatment, especially in patients with multiple comorbidities. The proposed award would enable her to continue mentoring while augmenting her research, specifically incorporating aims built to address key knowledge gaps regarding the oral anticoagulant and antiplatelet therapy. The new research proposed herein is builds on ongoing work to create unique and much needed patient oriented research (POR) training opportunities within the evolving landscape of oral antithrombotic therapy and integrates pharmacogenomics and implementation of precision medicine. The candidate's NHLBI R01 grant along with the three new projects will form the basis for the mentee training. Each project is led by a mentee. PROJECT1 will elucidate the influence of heart failure as defined as left ventricular ejection fraction (LVEF <40%) on warfarin response. PROJECT 2: will evaluate the influence of clinical and genetic (candidate genes) on Dabigatran (DBG) related hemorrhage and build clinical prediction rules to personalize the prediction of hemorrhage among DBG users. PROJECT 3: will evaluate the effectiveness of genotype-guided antiplatelet therapy (GGAT) on complications following percutaneous coronary intervention and assess its clinical utility and economic value. Mentorship aims expanding the POR training opportunities for MD, Pharm.D, and PhD trainees. Mentees will lead the new projects, conduct analysis and publish original research. They will leverage this to propose new research as part of their NIH- K23 applications. In the strongly supportive and collaborative environment of UAB, this award will ensure Dr. Limdi continues to grow her research program, and build capacity in POR by mentoring junior investigators to build their own careers. The breadth and depth of the multiple institutional programs, UAB's CTSA and her leadership in UAB's Personalized Medicine Institute will provide the resources and the foundation to advance precision cardiovascular medicine.
Clinical, genetic and environmental factors that predict individual variability in antithrombotic response can help identify patients who stand to benefit or be harmed by these drugs. However, the integration of these predictors into clinical decision making requires a paradigm shift based on evidence of their benefit vs. risk (clinical utility) and value (cost-effectiveness). To facilitate this paradigm shift we propose to incorporate genetic information with environmental and clinical predictors to help develop patient-focused and population-based preventive and therapeutic guidelines for ?Personalized Antithrombotic Therapy (PAT).?
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