"The Impact of Pharmacogenetics on Patient Response to Clopidogrel Post-Coronary Angioplasty: Systematic Review"
DOI:
https://doi.org/10.69980/ajpr.v28i5.661Keywords:
Pharmacogenetics; CYP2C19; Clopidogrel; Coronary Angioplasty; Percutaneous Coronary Intervention (PCI); Antiplatelet Therapy; Genetic Polymorphism; Personalized Medicine; Platelet Reactivity; Precision Cardiology.Abstract
Background Clopidogrel is widely used post-percutaneous coronary intervention (PCI), but patient response varies significantly due to genetic polymorphisms, particularly in the CYP2C19 gene. Loss-of-function alleles reduce the conversion of clopidogrel to its active form, compromising its efficacy and increasing cardiovascular risks.
Objective To systematically review the impact of CYP2C19 polymorphisms on clopidogrel response and cardiovascular outcomes in adult PCI patients.
Methods A PRISMA-guided systematic review was conducted using PubMed, Embase, Web of Science, Scopus, and Cochrane Library. Studies included were published from 2000 to 2025, involved human adults post-PCI on clopidogrel, and reported outcomes based on CYP2C19 genotype. Data were synthesized narratively due to study heterogeneity.
Results Fifteen studies involving over 20,000 patients were included. CYP2C19 LOF allele carriers had increased rates of stent thrombosis, MACE, and reduced platelet inhibition. Genotype-guided therapy (e.g., ticagrelor or high-dose clopidogrel) significantly improved clinical outcomes in LOF carriers.
Conclusion Pharmacogenetic testing for CYP2C19 variants can optimize clopidogrel therapy post-PCI. Incorporating genotype-guided treatment strategies enhances safety and efficacy, supporting the case for precision medicine in cardiology.
References
1. Al-Rubaish, A. M., et al. (2020). Bedside CYP2C19 testing in PCI patients: Implementation outcomes. BMC Cardiovascular Disorders, 20(1), 487. https://doi.org/10.1186/s12872-020-01558-2
2. Amarapalli, J., Sharma, P., Datta, R., & Sharma, A. (2023). Implications of pharmacogenetic testing for clopidogrel therapy in a tertiary healthcare hospital in North India. Cureus, 15(7), e42169. https://doi.org/10.7759/cureus.42169
3. Angulo-Aguado, M., Panche, K., Tamayo-Agudelo, C. A., Ruiz-Torres, D. A., Sambracos-Parrado, S., Niño-Orrego, M. J., Páez, N., Piñeros-Hernandez, L. B., Castillo-León, L. F., Pardo-Oviedo, J. M., Abaunza, K. P., Laissue, P., Contreras, N., Calderón-Ospina, C. A., & Fonseca-Mendoza, D. J. (2021). A pharmacogenetic study of CYP2C19 in acute coronary syndrome patients of Colombian origin reveals new polymorphisms potentially related to clopidogrel therapy. Journal of Personalized Medicine, 11(5), 400. https://doi.org/10.3390/jpm11050400
4. Biswas, M., et al. (2021). MACE risk in CYP2C19 LOF carriers using PPIs and clopidogrel. International Journal of Clinical Pharmacy, 43(3), 803–812. https://doi.org/10.1007/s11096-021-01261-y
5. Brown, S. A., & Pereira, N. (2018). Pharmacogenomic impact of CYP2C19 variation on clopidogrel therapy in precision cardiovascular medicine. Journal of Personalized Medicine, 8(1), 8. https://doi.org/10.3390/jpm8010008
6. Castrichini, M., Luzum, J. A., & Pereira, N. (2023). Pharmacogenetics of antiplatelet therapy. Annual Review of Pharmacology and Toxicology, 63, 211–229. https://doi.org/10.1146/annurev-pharmtox-051921-092701
7. Cuisset, T., et al. (2012). Pharmacogenetics of clopidogrel in ACS patients. Human Genetics, 131, 653–665. https://doi.org/10.1007/s00439-011-1130-6
8. Duarte, J. D., & Cavallari, L. H. (2021). Pharmacogenetics to guide cardiovascular drug therapy. Nature Reviews Cardiology, 18, 161–173. https://doi.org/10.1038/s41569-021-00549-w
9. Elsayed, M., et al. (2025). Comparison between clopidogrel and ticagrelor in CYP2C19 loss-of-function alleles: A meta-analysis. European Journal of Clinical Pharmacology. https://doi.org/10.1007/s00228-025-03860-4
10. Fathy, S., Shahin, M. H., Langaee, T., Khalil, B. M., Saleh, A., Sabry, N. A., Schaalan, M. F., El Wakeel, L. L., & Cavallari, L. H. (2018). Pharmacogenetic and clinical predictors of response to clopidogrel plus aspirin after acute coronary syndrome in Egyptians. Pharmacogenetics and Genomics, 28(9), 207–213. https://doi.org/10.1097/FPC.0000000000000349
11. Haj Saleh, N., & Youssef, L. A. (2025). The frequencies of CYP2C19 alleles and clinical efficacy of double-dose clopidogrel in Syrian patients. BMC Cardiovascular Disorders. https://doi.org/10.1186/s12872-025-04768-8
12. Hernandez-Suarez, D. F., Botton, M. R., Scott, S. A., Tomey, M. I., Garcia, M. J., Wiley, J., Villablanca, P. A., Melin, K., Lopez-Candales, A., Renta, J. Y., & Duconge, J. (2018). Pharmacogenetic association study on clopidogrel response in Puerto Rican Hispanics with cardiovascular disease: A novel characterization of a Caribbean population. Pharmacogenomics and Personalized Medicine, 11, 95–106. https://doi.org/10.2147/PGPM.S165805
13. Lee, S. H., Jeong, Y., Hong, D., Choi, K. H., Lee, J. M., Park, T. K., Yang, J. H., Hahn, J., Choi, S., Gwon, H., Jeong, M. H., Kim, B., Joo, H. J., Chang, K., Park, Y., Ahn, S. G., Suh, J., Lee, S. Y., Cho, J. R., ... Song, Y. B. (2023). Clinical impact of CYP2C19 genotype on clopidogrel-based antiplatelet therapy after percutaneous coronary intervention. JACC: Cardiovascular Interventions, 16(7), 829–843. https://doi.org/10.1016/j.jcin.2023.01.363
14. Mahdieh, N., et al. (2018). Clopidogrel pharmacogenetics in Iranian PCI patients. Cardiovascular Toxicology, 18(6), 501–508. https://doi.org/10.1007/s12012-018-9459-x
15. Morales-Rosado, J. A., et al. (2021). Next-generation sequencing of CYP2C19 in stent thrombosis. Drugs & Therapy Perspectives, 37, 155–161. https://doi.org/10.1007/s10557-020-06988-w
16. Novkovic, M., et al. (2018). CYP2C19 genotype and bleeding in Serbian STEMI patients. European Journal of Clinical Pharmacology, 74(3), 331–337. https://doi.org/10.1007/s00228-017-2401-5
17. Patel, T. J., et al. (2025). Implementing CYP2C19-guided clopidogrel therapy: A scoping review. Journal of Personalized Medicine. https://doi.org/10.1038/s41397-025-00371-4
18. Pereira, N. L., Rihal, C. S., So, D. Y. F., Rosenberg, Y., Lennon, R. J., Mathew, V., Goodman, S. G., Weinshilboum, R. M., Wang, L., Baudhuin, L. M., Lerman, A., Hasan, A., Iturriaga, E., Fu, Y. P., Geller, N., Bailey, K., & Farkouh, M. E. (2019). Clopidogrel pharmacogenetics. Circulation: Cardiovascular Interventions, 12(4), e007811. https://doi.org/10.1161/CIRCINTERVENTIONS.119.007811
19. Russmann, S., et al. (2021). Implementation of CYP2C19 pharmacogenetics in clinical practice. European Journal of Clinical Pharmacology, 77(3), 417–426. https://doi.org/10.1007/s00228-020-03050-4
20. Sharma, R., et al. (2024). CYP2C19 variants and clinical outcomes in CAD patients on clopidogrel: A meta-analysis. International Journal of Cardiology. https://doi.org/10.1016/j.ijcard.2024.01.013
21. Wang, Z., et al. (2019). Two CYP2C19 mutations and platelet aggregation in Chinese PCI patients. Journal of Human Genetics, 64, 1–10. https://doi.org/10.1038/s41397-018-0036-2
22. Zhang, L., et al. (2015). Effect of high-dose clopidogrel by genotype in PCI patients: Meta-analysis. Thrombosis Research, 135(1), 65–71. https://doi.org/10.1016/j.thromres.2014.10.029
Downloads
Published
Issue
Section
License
Copyright (c) 2025 American Journal of Psychiatric Rehabilitation
This work is licensed under a Creative Commons Attribution 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International License permitting all use, distribution, and reproduction in any medium, provided the work is properly cited.
