1175. Pharmacogenomic considerations for antiplatelet agents: the era of precision medicine in stroke prevention and neurointerventional practice

Authors: Phillip A. Bonney, MD; Brian Walcott, MD; Ben Yim, MD; Waleed Brinjikji, MD (Los Angeles, CA)

Introduction: Antiplatelet drugs are widely utilized in the setting of primary stroke prevention, secondary stroke prevention, and neuroendovascular device-related stroke prevention. Typical treatment in such cases consists of dual antiplatelet therapy with aspirin and a P2Y12 adenosine diphosphate receptor inhibitor. While these medications are effective in general, variability exists in drug activity between patients. This is in large part due to genotypic differences in drug metabolism. Methods: To better understand the pharmacogenetic underpinnings of resistance to antiplatelet agents, the PharmGKB database was mined to identify genetic variants with potential clinical relevance for response to aspirin, clopidogrel, prasugrel, and ticagrelor. Reports were cross-referenced with original source manuscripts. Annotated variants were then sorted based on levels of evidence. Only the highest quality of annotations (levels 1 and 2) were used for reporting purposes. If high quality annotations did not exist, the next two levels of evidence were reported. Additionally, a review of relevant cardiovascular literature was conducted to identify studies factoring pharmacogenetics into antiplatelet selection. Results: Variants were reported for all drugs. The highest level of evidence was found in cytochrome P450 (CYP450) genotypes affecting response to clopidogrel. Multiple reports noted significant rates of clopidogrel resistance among study populations, approaching up to 50%. Recent work in the cardiovascular literature has successfully used genotyping to identify clopidogrel non-responders, with decreased thrombotic complications stemming from use of prasugrel or ticagrelor in these populations. Conclusion: Individual genetic influences have an impact on the pharmacodynamics of antiplatelet agents. While current clinical practice for stroke prevention is primarily empiric or guided by functional assays, there now exists a third potential pathway to base treatment decisions: genotype-guided treatment.