Brittney Davis, PharmD., assistant professor in the UAB Department of Neurology, recently received a five-year, K23 grant from the National Heart, Lung, and Blood Institute of the NIH to study sex-specific pharmacogenomic and metabolomic factors related to adverse effects of anticoagulants, commonly known as blood thinners. The award amount is $818,838 starting in September 2024.
According to Davis, anticoagulants are among the most frequently prescribed medications in the U.S.; however, patients sometimes experience adverse effects associated with the medications, such as clotting and bleeding.
“Anticoagulants are a leading drug class responsible for patient harm and are the target of a national action plan to prevent adverse drug events,” Davis said. “Response to anticoagulants also varies by sex, with females reaching higher drug levels and experiencing more bleeding complications compared to males.”
Davis explained that historically, clinical drug trials have included fewer women and have not analyzed sex-specific data. This has led to gaps in researchers’ understanding as to how anticoagulants affect females—an issue that has been recognized at the federal level as a threat to ensuring the safety of women taking these medications.
“Furthermore, recent evidence suggests that sex-specific differences in gene expression and metabolite profiles may play a critical role in medication response,” Davis added. “Over 75 genes involved in drug response are expressed differently in males and females, potentially leading to sex-related differences in drug metabolism, drug transport, and the occurrence of adverse drug events.”
Davis explains what motivated her to pursue this research, and what she hopes to achieve.
What inspired you to conduct this research?
Davis: The realization that females have been underrepresented in clinical trials, that they exhibit different responses to anticoagulants, that there are sex-specific genetic and metabolic factors that contribute to response, yet sex-specific assessments are not commonly conducted, in addition to the potential harm that can result from variable anticoagulant response inspired me to pursue this research. Pharmacogenomics, the study of how a person’s genes affect how they respond to medicines, may help us understand why some people might respond better to a drug than others, or why some people might experience side effects. Additionally, metabolomics, the study of metabolites in the body, can provide insights into how the body functions or responds to certain treatments by helping understand chemical changes that occur. By identifying sex-specific pharmacogenomic and metabolomic factors associated with anticoagulant response, this research aims to further our understanding of sex-related variability in drug response and help personalize and optimize anticoagulant therapy.
What are your goals for the research this grant will support?
Davis: Overall, the goal of this research is to identify and evaluate pharmacogenomic markers and metabolite profiles associated with differences in response to anticoagulants. This includes examining drug levels (pharmacokinetics), biomarker levels (pharmacodynamics), and clinical bleeding events, with a focus on identifying sex-specific predictors. Investigating sex-specific mechanisms could provide new insights into underlying predictors or pathways involved in variable anticoagulant response and be used to target drug and biomarker threshold concentrations. This can allow for the development of personalized treatment strategies, enhance safety and efficacy, improve drug selection and dosing, and reduce the likelihood of bleeding complications for patients treated with anticoagulants.
How do you hope this research will positively impact patients?
Davis: It has the potential to improve how anticoagulants are prescribed and managed by enabling the development of personalized treatment strategies. These strategies could improve drug dosing and selection, as well as lead to the establishment of thresholds and tools to predict therapeutic and adverse medication responses based on an individual’s genetic and metabolic profiles. This personalized approach would allow patients to receive treatments tailored to their specific needs, resulting in improved anticoagulant safety and efficacy. In the long term, insights gained from this research could help predict whether a patient is likely to have a positive response or experience adverse effects, providing valuable tools for monitoring and adjusting treatment to achieve the best possible outcomes for patients.
How do you hope this research will inspire advancements in the field?
Davis: The goal is to foster the development of clinical tools and more individualized treatment protocols that could promote the wider adoption of precision medicine in clinical practice and transform how clinicians manage anticoagulant therapy. Furthermore, I hope this research will not only deepen our understanding of anticoagulant therapy, but also catalyze a broader shift toward both sex-specific and integrative pharmacogenomic and metabolomic approaches to assess complex drug responses. This could inspire further research adopting similar approaches and drive precision medicine innovation and advancement in both clinical practice and scientific research.