Pharmacogenomic considerations for antiplatelet agents: the era of precision medicine in stroke prevention and neurointerventional practice
- PMID: 30936195
- PMCID: PMC6549574
- DOI: 10.1101/mcs.a003731
Pharmacogenomic considerations for antiplatelet agents: the era of precision medicine in stroke prevention and neurointerventional practice
Abstract
Antiplatelet drugs are widely utilized in the setting of primary stroke prevention, secondary stroke prevention, and neuroendovascular device-related stroke prevention. These medications are effective in general, although significant variability in drug activity exists between patients. Although this variation may be related in part to a multitude of factors, a growing body of evidence suggests that individual genotypes are a main contributor. The PharmGKB database was mined to prioritize genetic variants with potential clinical relevance for response to aspirin, clopidogrel, prasugrel, and ticagrelor. Although variants were reported for all drugs, the highest level of evidence was found in cytochrome P450 (CYP450) genotype variation related to clopidogrel response. Individual genetic influences have an impact on the pharmacodynamics of antiplatelet agents. Current clinical practice for stroke prevention is primarily empiric or guided by functional assays; however, there now exists a third potential pathway to base treatment decisions: genotype-guided treatment.
© 2019 Bonney et al.; Published by Cold Spring Harbor Laboratory Press.
References
-
- Anselmi CV, Briguori C, Roncarati R, Papa L, Visconti G, Focaccio A, De Micco F, Latronico MV, Pagnotta P, Condorelli G. 2013. Routine assessment of on-clopidogrel platelet reactivity and gene polymorphisms in predicting clinical outcome following drug-eluting stent implantation in patients with stable coronary artery disease. JACC Cardiovasc Interv 6: 1166–1175. 10.1016/j.jcin.2013.06.010 - DOI - PubMed
-
- Bergmeijer TO, Reny J-L, Pakyz RE, Gong L, Lewis JP, Kim E-Y, Aradi D, Fernandez-Cadenas I, Horenstein RB, Lee MTM, et al. 2018. Genome-wide and candidate gene approaches of clopidogrel efficacy using pharmacodynamic and clinical end points—Rationale and design of the International Clopidogrel Pharmacogenomics Consortium (ICPC). Am Heart J 198: 152–159. 10.1016/j.ahj.2017.12.010 - DOI - PMC - PubMed
-
- Best PJ, Steinhubl SR, Berger PB, Dasgupta A, Brennan DM, Szczech LA, Califf RM, Topol EJ, CREDO Investigators. 2008. The efficacy and safety of short-and long-term dual antiplatelet therapy in patients with mild or moderate chronic kidney disease: results from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial. Am Heart J 155: 687–693. 10.1016/j.ahj.2007.10.046 - DOI - PubMed
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