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Clinical Impact of CYP2C19 Genotype on Clopidogrel-Based Antiplatelet Therapy After Percutaneous Coronary Intervention

https://doi.org/10.1016/j.jcin.2023.01.363Get rights and content

Abstract

Background

Although there is a growing body of evidence that CYP2C19 genotyping can be beneficial when considering treatment with clopidogrel after percutaneous coronary intervention (PCI), whether a genotype-guided strategy can be generally adopted in routine practice remains unclear among East Asians.

Objectives

This study sought to investigate long-term outcomes of patients undergoing clopidogrel-based antiplatelet therapy after drug-eluting stent (DES) implantation according to CYP2C19 genotypes.

Methods

From the nationwide multicenter PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) consortium, patients who underwent CYP2C19 genotyping were selected and classified according to CYP2C19 loss-of-function allele: rapid metabolizers (RMs) or normal metabolizers (NMs) vs intermediate metabolizers (IMs) or poor metabolizers (PMs). The primary outcome was a composite of cardiac death, myocardial infarction, and stent thrombosis at 5 years after the index procedure.

Results

Of 8,163 patients with CYP2C19 genotyping, 56.7% presented with acute coronary syndrome. There were 3,098 (37.9%) in the RM or NM group, 3,906 (47.9%) in the IM group, and 1,159 (14.2%) in the PM group. IMs or PMs were associated with an increased risk of 5-year primary outcome compared with RMs or NMs (HRadj: 1.42; 95% CI: 1.01-1.98; P = 0.041), and the effect was more pronounced in the first year (HRadj: 1.67; 95% CI: 1.10-2.55; P = 0.016). The prognostic implication of being an IM and PM was significant in acute coronary syndrome patients (HRadj: 1.88; 95% CI: 1.20-2.93; P = 0.005) but not in those with stable angina (HRadj: 0.92; 95% CI: 0.54-1.55; P = 0.751) (interaction P = 0.028).

Conclusions

Among East Asians with clopidogrel-based antiplatelet therapy after DES implantation, CYP2C19 genotyping could stratify patients who were likely to have an increased risk of atherothrombotic events. (Platelet Function and genoType-Related Long-term progGosis in DES-treated Patients: A Consortium From Multi-centered Registries [PTRG-DES]; NCT04734028)

Section snippets

Study population

The PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) consortium comprises of 9 prospective registries from 32 Korean academic centers, endorsed by the Korean Society of Interventional Cardiology.22 The participating registries and centers are listed in Supplemental Table 1. It was specifically designed to determine the relationship between platelet reactivity/genotyping and subsequent clinical events in East Asian patients with coronary artery

Baseline characteristics

The baseline characteristics are described in Table 1 and Supplemental Table 4. Of 8,163 patients with CYP2C19 genotyping and clopidogrel-based antiplatelet therapy after DES implantation, 3,098 (37.9%) patients were RMs or NMs, 3,906 (47.9%) patients were IMs, and 1,159 (14.2%) were PMs. The mean age of the study population was 64.2 ± 10.8 years, 65.1% were men, and 56.7% presented with ACS. There was no significant difference in demographics, cardiovascular risk factors, or laboratory

Discussion

The present study evaluated the prognostic impact of CYP2C19 genotyping for clopidogrel-based antiplatelet therapy among East Asian patients with stable IHD or ACS after DES implantation using a nationwide and multicenter consortium. The major findings were as follows: 1) only 37.9% of the patients in Korea were RMs or NMs; 2) PRU levels and the prevalence of HPR increased proportionally according to the number of CYP2C19 loss-of-function allele; 3) CYP2C19 genotyping could be helpful for

Conclusions

In this large real-world data composing East Asians who underwent DES implantation and clopidogrel-based antiplatelet therapy, IMs or PMs showed a higher risk of cardiac death, myocardial infarction, and stent thrombosis at 5-year follow-up compared with RMs or NMs. The prognostic implication of CYP2C19 genotyping was more evident for patients with ACS than for those with stable IHD or in the early phase (within 1 year) after DES implantation. De-escalation to clopidogrel monotherapy should be

Funding Support and Author Disclosures

The study was sponsored by the Platelet-Thrombosis Research Group under the Korean Society of Intervention Cardiology. Dr Jeong has received honoraria for lectures from AstraZeneca, Daiichi Sankyo, Sanofi, Han-mi Pharmaceuticals, and Yuhan Pharmaceuticals; and research grants or support from Yuhan Pharmaceuticals and U&I Corporation. Dr Joo has received honoraria for lectures from AstraZeneca, Hanmi, Samjin, Dong-A, HK inno. N Pharmaceuticals, and DIO Medical Ltd. Dr Song has received honoraria

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    The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.

    Drs Lee and Jeong contributed equally to this work.

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