Advanced Researcher Cipherome, Inc San Jose, California, United States
Background: Clopidogrel is a commonly prescribed antiplatelet drug for myocardial infarction (MI) activated by a specific gene called CYP2C19, and patients with variants in the gene are at risk of clopidogrel being ineffective or over-effective with adverse reactions. Since the percentage of CYP2C19 variation exists up around 30% depending on the ethnicities, an appropriate alternative prescription according to genotype is strongly needed. Methods: We performed survival analysis on 7406 subjects prescribed clopidogrel and 821 subjects prescribed ticagrelor or prasugrel using the UK Biobank with genetic data. Subjects admitted through the emergency department with myocardial infarct within one year after the first prescription were labeled as having cardiovascular events. We compared the cumulative incidence of cardiovascular events across genotypes and drug types with Kaplan-Meier curve. Results: Among clopidogrel participants, LoF patients had a higher proportion of MI compared to normal participants(Normal 10.56%, LoF 11.67%), while LoF patients had a lower incidence of MI in the group prescribed ticagrelor or prasugrel(Normal 21.56%, LoF 19.51%). Conclusion: A significant number of UK Biobank participants have CYP2C19 LoF variants which can significantly affect clopidogrel drug response. CYP2C19 LoF variants are more likely to have higher incidence of MI even with clopidogrel prescription. CYP2C19 must be considered to optimize the drug response to commonly prescribed antiplatelets, including clopidogrel, ticagrelor and prasugrel. Future work includes exploring the bleeding risk of the antiplatelets as well as other genotypes of CYP2C19 or genes associated with antiplatelet metabolism.
Pilling LC, Türkmen D, Fullalove H, et al. Analysis of CYP2C19 genetic variants with ischaemic events in UK patients prescribed clopidogrel in primary care: a retrospective cohort study. BMJ Open 2021;11:e053905. doi:10.1136/ bmjopen-2021-053905
