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Clopidogrel Resistance and P2y12 Receptor Gene Polymorphisms in Patients with Non-ST Elevated Acute Coronary Syndrome

1Bukovinian State Medical University, Internal Medicine, Clinical Pharmacology and Occupational Diseases, Chernivtsy, Ukraine, 2Bukovinian State Medical University, Chernivtsy, Ukraine

Abstract Number: PB0001

Meeting: ISTH 2020 Congress

Theme: Arterial Thromboembolism » Acute Coronary Syndromes

Background: The prevalence of antiplatelet drug resistance during antiplatelet therapy varies from 20% to 45% for clopidogrel usage. The reasons and risk factors of this state are not completely known. As P2Y12 receptor plays key role in platelet activation and data on its role for clopidogrel resistance is inconsistent the study of this gene polymorphisms is actual and perspective.

Aims: The aim of this study was to investigate the association of P2Y12 polymorphisms and clopidogrel resistance due to the platelet aggregation at patients with non-ST elevated acute coronary syndrome.

Methods: 200 patients with non-ST elevated acute coronary syndrome from Bukovinian region (Ukraine) were genotyped in order to the H1(744T) and H2 (744C) haplotypes of the P2Y12 receptor gene. Aggregation studies with J.Born method. Decreasing of ADP-induced platelet aggregation < 10%, 10-29%, and ≥30% compared to the basal level considered as “clopidogrel resistance”, “partial clopidogrel resistance” or “clopidogrel sensitiveness”.

Results: In addition to specific genotype presentation (H1/H1; H1/H2; H2/H2) we have divided patients into the groups: homozygotes with H1/H1 (68 persons, 34,0%), homozygotes with H2/H2 mutation (18 persons, 9,0%) and heterozygotes H1/H2 (114 persons, 57%).
The spontaneous and ADP-induced aggregation of platelets after 7 days of dual antiplatelet therapy was significantly higher in H1/H2 and H2/H2 genotypes in compare to the H1/H1 genotype (p,p1< 0,05). The time of aggregation was shortest in mutant H2/H2 genotype (p< 0,05). The higher incidence of “clopidogrel resistance” and “partial clopidogrel resistance” patients was registered in H2/H2 genotype (odds ratio - 9,72), and, also, in H1/H2 genotype (odds ratio - 3,55), Mantel-Haenszel χ2 – 20,62, p< 0,001. Generalized odds ratio (Agresti´s alpha) was 3,746
[CI95%2,122-6,613].

Conclusions: This study supports the association of P2RY12 gene polymorphisms with platelet aggregation level, platelet dysfunction and higher incidence of “clopidogrel resistance” in genotypes H2/H2 and H1/H2 at patients with non-ST elevated acute coronary syndrome.

To cite this abstract in AMA style:

Shorikova D, Shorikov E, Shorikov P. Clopidogrel Resistance and P2y12 Receptor Gene Polymorphisms in Patients with Non-ST Elevated Acute Coronary Syndrome [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/clopidogrel-resistance-and-p2y12-receptor-gene-polymorphisms-in-patients-with-non-st-elevated-acute-coronary-syndrome/. Accessed September 22, 2023.

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