Association of CYP2C19*2 Polymorphism with Clopidogrel Response and 1-year Major Adverse Cardiovascular Events in A Multiethnic Population with Drug-Eluting Stents

Abstract

Background: Patients undergoing elective percutaneous coronary intervention (PCI) with drug-eluting stents (DES) who have impaired clopidogrel response, have a higher risk of subsequent major adverse cardiovascular events (MACE). Aim of the study: To establish the relationship between CYP2C19 genotype, clopidogrel responsiveness and 1–year MACE. Materials & methods: Aspirin/clopidogrel responses were assessed with Multiplate Analyzer and CYP2C19*2 allele by SpartanRx. Results: A total of 42.0% carried ≥1 CYP2C19*2 allele. Prevalences of aspirin and clopidogrel high on-treatment platelet reactivity (HPR; local cutoffs: 300 AU*min for aspirin and 600 AU*min for clopidogrel) were 11.5% and 19.8% respectively. In multivariate ana­lysis, clopidogrel HPR was found to be an independent predictor for 1–year MACE (adj HR: 3.48, p = 0.022 ). Conclusion: Having clopidogrel HPR could be a potentially modifiable risk factor guided by phenotyping.

Keywords::

• CYP2C19*2 genetic polymorphism
• double antiplatelet therapy
• percutaneous coronary intervention
• platelet function test

Acknowledgements

We would like to thank the participants, nurses, pharmacists, doctors and colleagues who were involved in this study, including Mr. Teck Long King for the statistical input. Moreover, we would like to express our gratitude to all reviewers for their invaluable comments in this manuscript. We would also like to thank the Director General of Health, Malaysia for his permission to publish this article.

Financial & competing interests disclosure

This study was supported by a grant from Ministry of Health Malaysia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This study was supported by a grant from Ministry of Health Malaysia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.