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. 2024 Jan 28;21(1):90-103.
doi: 10.26599/1671-5411.2024.01.004.

Effect of cytochrome P450 2C19 (CYP2C19) gene polymorphism and clopidogrel reactivity on long term prognosis of patients with coronary heart disease after PCI

Cheng-Yan Hu  1 , Yan-Ling Wang  2 , Zhen-Xing Fan  2 , Xi-Peng Sun  2 , Shuai Wang  2   3 , Zhi Liu  3
Affiliations

Effect of cytochrome P450 2C19 (CYP2C19) gene polymorphism and clopidogrel reactivity on long term prognosis of patients with coronary heart disease after PCI

Cheng-Yan Hu et al. J Geriatr Cardiol. .

Abstract

Objective: To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with long-term clinical outcome in patients with coronary heart disease (CHD) undergoing percutaneous coronary intervention (PCI).

Methods: In total, 675 patients were enrolled. Based on the platelet inhibition rate, patients were categorized into two groups: clopidogrel low responsiveness (CLR) and normal clopidogrel responsiveness (NCR). The CLR group was divided into ticagrelor and clopidogrel group based on the antiplatelet drugs used in the follow-up treatment. Patients were classified into three groups (normal metabolizer, intermediate metabolizer, and poor metabolizer) based on the CYP2C19 genotype. We aimed to evaluate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity. The cumulative rates of 12-month all-cause deaths, major adverse cardiovascular events (MACCEs), and bleeding events were calculated.

Results: CLR was observed in 44.4% of the overall population. Significant differences were observed in the platelet inhibition rate of clopidogrel among the three metabolic genotypes (P < 0.05). At the 12-month follow-up, 13 patients (1.9%) died and 96 patients (14.2%) experienced MACCEs. Patients with CLR (9.6% vs. 11.7% vs. 22.1%, P < 0.05) or poor metabolizer (10.7% vs. 16.4% vs. 22.6%, P = 0.026) experienced a higher rate of MACCEs. A MACCEs risk score between zero and two was calculated. The highest incidence of MACCEs significantly increased with the 2-positive results, and the area under the curve (AUC) was 0.712 (95% CI: 0.650-0.774, P < 0.05). There was no significant difference between the group with a score of one and the occurrence of MACCEs (P > 0.05).

Conclusions: Low response to clopidogrel in CHD patients is correlated with CYP2C19 gene polymorphism. CYP2C19 genotyping combined with platelet reactivity is an independent predictor of 12-months MACCEs in patients with clopidogrel treatment after PCI, which is better than either test alone.

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Figures

Figure 1
Figure 1
Flow chart of the study.
Figure 2
Figure 2
Clopidogrel reactivity and CYP2C19 gene.
Figure 3
Figure 3
Comparison of clinical outcomes in the overall population at 12-month follow-up.
Figure 4
Figure 4
Comparison of Clinical outcomes with different CYP2C19 genotypes at 12-month follow-up.
Figure 5
Figure 5
Relationships between MACCEs and the aggregate positive results of CYP2C19 genotyping and on-clopidogrel platelet reactivity.
See this image and copyright information in PMC

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References

    1. Levine GN, Bates ER, Bittl J A, et al 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016;68:1082–1115. doi: 10.1016/j.jacc.2016.03.513. - DOI - PubMed
    1. Mejin M, Tiong WN, Lai LY, et al CYP2C19 genotypes and their impact on clopidogrel responsiveness in percutaneous coronary intervention. Int J Clin Pharm. 2013;35:621–628. doi: 10.1007/s11096-013-9783-y. - DOI - PubMed
    1. Yi X, Lin J, Zhou Q, et al Clopidogrel resistance increases rate of recurrent stroke and other vascular events in Chinese population. J Stroke Cerebrovasc Dis. 2016;25:1222–1228. doi: 10.1016/j.jstrokecerebrovasdis.2016.02.013. - DOI - PubMed
    1. Buonamici P, Marcucci R, Migliorini A, et al Impact of platelet reactivity after clopidogrel administration on drug-eluting stent thrombosis. J Am Coll Cardiol. 2007;49:2312–2317. - PubMed
    1. Sibbing D, Braun S, Morath T, et al Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis. J Am Coll Cardiol. 2009;53:849–856. doi: 10.1016/j.jacc.2008.11.030. - DOI - PubMed

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