Research Article

Multiple genetic mutations increase the risk of thrombosis associated with clopidogrel after percutaneous coronary intervention

Department of Pharmacy, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, 200240, China

‡Authors contributed equally

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Jinfei Song‡

Department of Pharmacy, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, 200240, China

‡Authors contributed equally

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Xiaoying Shen

Department of Pharmacy, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, 200240, China

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Qing Liang

https://orcid.org/0000-0002-3281-2607

Department of Pharmacy, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, 200240, China

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Guangchun Sun

**Author for correspondence:

E-mail Address: sunguangchun@5thhospital.com

https://orcid.org/0000-0002-5879-1621

Department of Pharmacy, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, 200240, China

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Yan Yu

*Author for correspondence:

E-mail Address: yanyu10@fudan.edu.cn

https://orcid.org/0000-0002-7152-8377

Department of Pharmacy, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, 200240, China

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Published Online:9 Mar 2023https://doi.org/10.2217/pgs-2022-0167

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Abstract

Background: The effect of multiple mutations in CYP2C19, PON1 and ABCB1 genes on the effectiveness and safety of dual antiplatelet therapy after percutaneous coronary intervention remains unclear. Methods: In total, 263 Chinese Han patients were enrolled in this study. Platelet aggregation rates and thrombosis risk were used to compare clopidogrel responses and outcomes in patients with different numbers of genetic mutations. Results: Our study demonstrated that 74% of the patients carried more than two genetic mutations. High platelet aggregation rates were associated with genetic mutations in patients receiving clopidogrel and aspirin after percutaneous coronary intervention. Genetic mutations were closely related to the recurrence of thrombotic events, but not bleeding. The number of genes that become dysfunctional in patients is directly correlated with the risk of recurrent thrombosis. Conclusion: Compared with CYP2C19 alone or the platelet aggregation rate, it is more helpful to predict clinical outcomes by considering the polymorphisms of all three genes.

Plain language summary

The effects of different combinations of mutations in the genes CYP2C19, PON1 and ABCB1 on the effectiveness and safety of dual antiplatelet therapy in patients who undergo percutaneous coronary intervention (PCI) are unclear. In total, 263 Chinese Han patients receiving 75 mg clopidogrel and 100 mg aspirin daily for 12 months after PCI were enrolled in this study. ADP-induced platelet aggregation rates, thrombosis and bleeding risk were used to compare clopidogrel responses among the patients. Only 3.4% of patients had no mutations in CYP2C19, PON1 or ABCB1, and 74% of patients who chose to be genetically tested carried more than two mutations in these genes. High ADP-induced platelet aggregation rates in patients receiving clopidogrel and aspirin after PCI were associated with mutations in CYP2C19, PON1 and ABCB1. Patients with double or triple genetic mutations in CYP2C19, PON1 or ABCB1 had a higher risk of thrombosis within 18 months of follow-up. We conclude that multiple genetic polymorphisms influence platelet reactivity, bleeding and thrombosis risk during dual antiplatelet therapy after PCI.

Tweetable abstract

Multiple genetic mutations influence platelet response and thrombosis risk with clopidogrel and aspirin after percutaneous coronary intervention.

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Vol. 24, No. 4

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History

Received 17 November 2022

Accepted 16 February 2023

Published online 9 March 2023

Published in print March 2023

Information

Keywords

Author contributions

Y Yu, G Sun and H Jin conceived and designed this study. Patient follow-up and data extraction were carried out by X Shen and H Jin. All statistical analysis was performed by J Song and was checked by H Jin. The manuscript was drafted by Y Yu, and critically reviewed and revised by Q Liang and G Sun.

Financial & competing interests disclosure

The study was supported by grants from the health and family commission of Shanghai Minhang District (2018MW03, mwyjyx05), Shanghai Municipal Health and Family Planning Commission (20194Y0258, 202040387) and the Fifth People’s Hospital of Shanghai (2018WYZT04, 2020WYZD01). 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.

Ethical conduct of research

The study was approved by the ethics committee of The Fifth People’s Hospital of Shanghai (approval no. 2018-192). All the authors followed the principles outlined in the Declaration of Helsinki for all human investigations. Informed consent for patient information to be published in this article was not obtained because this was a retrospective study.

Data sharing statement

The original results of the retrospective study could be provided under request.

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