Comparison Between Clopidogrel and Prasugrel Associated With &lt;i&gt;CYP2C19&lt;/i&gt; Genotypes in Patients Receiving Percutaneous Coronary Intervention in a Japanese Population

Sawayama, Yuichi; Yamamoto, Takashi; Tomita, Yukinori; Asada, Kohei; Yagi, Noriaki; Fukuyama, Megumi; Miyamoto, Akashi; Ozawa, Tomoya; Isono, Tetsuichiro; Hira, Daiki; Takato, Tsuyoshi; Horie, Minoru; Nakagawa, Yoshihisa

doi:10.1253/circj.cj-20-0254

Cited by 14 publications

(4 citation statements)

References 18 publications

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“…In addition to the clinical factors, the CYP2C19 LOF allele is an important determinant of HPR. In this study, extensive, intermediate, and poor metabolizers were found in 30.4%, 52.7%, and 16.8% of patients, in line with previous reports 31) . The CYP2C19 LOF allele is well known to be associated with a marked decrease in the platelet response to clopidogrel, as also shown in this study, resulting in a significant interpatient variability of platelet reactivity 32) .…”

Section: Impact Of Clinical and Genetic Factors On Hprsupporting

confidence: 93%

Differential Impact of Clinical and Genetic Factors on High Platelet Reactivity in Patients with Coronary Artery Disease Treated with Clopidogrel and Prasugrel

Saito

Nishi

Wakabayashi

et al. 2022

JAT

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High platelet reactivity (HPR) is associated with increased risks of thrombotic events in patients with coronary artery disease. The recently developed ABCD-GENE score identified five clinical and genetic factors (age, body mass index, chronic kidney disease, diabetes, and the CYP2C19 loss-of-function allele) for HPR, although the significance of various stages of each factor is unclear.Methods: Four prospective studies were pooled, in which platelet reactivity was measured using the VerifyNow assay with clopidogrel and prasugrel; genotyping of CYP2C19 was also performed. Each component of the ABCD-GENE score was divided into three subcategories. VerifyNow P2Y12 reactivity units 208 were defined as HPR.Results: A total of 184 patients were included, of which 111 (60%) and 51 (28%) had HPR with clopidogrel and prasugrel. Chronic kidney disease had an impact on HPR on both clopidogrel and prasugrel, whereas the impact of diabetes was more evident in patients treated with prasugrel. Although the number of CYP2C19 lossof-function alleles was clearly associated with a likelihood of HPR with clopidogrel, P2Y12 reactivity units with prasugrel treatment were also significantly and progressively higher in patients with more CYP2C19 loss-offunction alleles.Conclusions: Clinical and genetic factors had a differential effect on a P2Y12 inhibitor reactivity with clopidogrel and prasugrel in patients with coronary artery disease. The severity of the factors also had a different impact on HPR.consisting of aspirin and a P2Y12 inhibitor, is the cornerstone of the antithrombotic regimen in patients undergoing PCI 2) . Currently, P2Y12 inhibitors of choice include clopidogrel, prasugrel, and ticagrelor 3) . Although clopidogrel is widely used in PCI, prasugrel and ticagrelor are the guideline-recommended P2Y12 inhibitors as a part of DAPT because of their potency Copyright©2021 Japan Atherosclerosis Society This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.

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Section: Impact Of Clinical and Genetic Factors On Hprsupporting

confidence: 93%

Differential Impact of Clinical and Genetic Factors on High Platelet Reactivity in Patients with Coronary Artery Disease Treated with Clopidogrel and Prasugrel

Saito

Nishi

Wakabayashi

et al. 2022

JAT

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“…Despite assessing several variants, no statistically significant association was observed between SNPs and outcomes among patients receiving prasugrel. Similar findings emerged from a single-center retrospective Japanese study on patients who had PCI [31]. Therefore, unlike clopidogrel, clinical results are unaffected by genetic variations in many candidate genes.…”

Section: Ticagrelor and Prasugrelsupporting

confidence: 70%

Pharmacogenomics of Cardiovascular Drugs for Atherothrombotic, Thromboembolic and Atherosclerotic Risk

Mauriello,

Ascrizzi,

Molinari

et al. 2023

Genes

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Purpose of Review: Advances in pharmacogenomics have paved the way for personalized medicine. Cardiovascular diseases still represent the leading cause of mortality in the world. The aim of this review is to summarize the background, rationale, and evidence of pharmacogenomics in cardiovascular medicine, in particular, the use of antiplatelet drugs, anticoagulants, and drugs used for the treatment of dyslipidemia. Recent findings: Randomized clinical trials have supported the role of a genotype-guided approach for antiplatelet therapy in patients with coronary heart disease undergoing percutaneous coronary interventions. Numerous studies demonstrate how the risk of ineffectiveness of new oral anticoagulants and vitamin K anticoagulants is linked to various genetic polymorphisms. Furthermore, there is growing evidence to support the association of some genetic variants and poor adherence to statin therapy, for example, due to the appearance of muscular symptoms. There is evidence for resistance to some drugs for the treatment of dyslipidemia, such as anti-PCSK9. Summary: Pharmacogenomics has the potential to improve patient care by providing the right drug to the right patient and could guide the identification of new drug therapies for cardiovascular disease. This is very important in cardiovascular diseases, which have high morbidity and mortality. The improvement in therapy could be reflected in the reduction of healthcare costs and patient mortality.

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“…This study was a retrospective observational study of consecutive patients who underwent PCI and who had their CYP2C19 variants assessed at Shiga University of Medical Science Hospital between September 2014 and August 2021. 15 CYP2C19 variants are determined in routine clinical practice when drugs that could be metabolized by CYP2C19, such as P2Y12-I or proton pump inhibitors, are used. In the present study, patients were regarded as having HBR when they satisfied at least 1 major and/or 2 minor ARC-HBR criteria.…”

Section: Data Source and Study Populationmentioning

confidence: 99%

“…Previous studies have shown that both clopidogrel and prasugrel are expected to be equally effective in preventing thrombotic events in CYP2C19 LOF non-carriers. 3,10, 15 In addition, prasugrel can prevent ischemic events after PCI without being affected by CYP2C19 LOF carrier or noncarrier status. 16 Therefore, we merged these populations (CYP2C19 LOF non-carriers prescribed clopidogrel and CYP2C19 LOF carriers and non-carriers prescribed prasugrel) as the group with retained P2Y12-I action and compared them to the group with decreased P2Y12-I action.…”

Section: Data Source and Study Populationmentioning

confidence: 99%

Clopidogrel Use in <i>CYP2C19</i> Loss-of-Function Carriers With High Bleeding Risk After Percutaneous Coronary Intervention

Sawayama

Tomita²,

Kohyama

et al. 2023

Circ J

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trials 2,3 and a meta-analysis 4 have shown that treatment with clopidogrel in CYP2C19 LOF carriers results in an increase in ischemic events after PCI compared with those treated with drugs that are less susceptible to CYP2C19, including prasugrel or ticagrelor. In this context, the US Food and Drug Administration has suggested an alternative P2Y12-I to clopidogrel for patients who are CYP2C19 poor metabolizers. 5 Recently, some populations receiving PCI have comprised patients with high bleeding risk (HBR). The Academic A P2Y12 inhibitor (P2Y12-I) in addition to aspirin is the cornerstone of treatment to reduce subsequent ischemic events in patients undergoing percutaneous coronary intervention (PCI). Clopidogrel, a conventional P2Y12-I, is a prodrug that undergoes metabolic transformation in the liver by cytochrome P450 (CYP) 2C19 to elicit its antiplatelet effect. A CYP2C19 loss-offunction (LOF) allele leads to a lower plasma concentration of the active clopidogrel metabolite, resulting in reduced inhibition of platelet aggregation. 1 Randomized control

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Comparison Between Clopidogrel and Prasugrel Associated With <i>CYP2C19</i> Genotypes in Patients Receiving Percutaneous Coronary Intervention in a Japanese Population

Abstract: Background:The association between cytochrome P450 (CYP) 2C19 genotypes and adverse events in patients treated with clopidogrel or prasugrel after percutaneous coronary intervention (PCI) in the Japanese population is unclear.

Cited by 14 publications

References 18 publications

Differential Impact of Clinical and Genetic Factors on High Platelet Reactivity in Patients with Coronary Artery Disease Treated with Clopidogrel and Prasugrel

Differential Impact of Clinical and Genetic Factors on High Platelet Reactivity in Patients with Coronary Artery Disease Treated with Clopidogrel and Prasugrel

Pharmacogenomics of Cardiovascular Drugs for Atherothrombotic, Thromboembolic and Atherosclerotic Risk

Clopidogrel Use in <i>CYP2C19</i> Loss-of-Function Carriers With High Bleeding Risk After Percutaneous Coronary Intervention

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