CYP2C19 Genotype Prevalence and Association With Recurrent Myocardial Infarction in British–South Asians Treated With Clopidogrel

Magavern, Emma F.; Jacobs, Benjamin; Warren, Helen; Finocchiaro, Gherardo; Finer, Sarah; van Heel, David A.; Smedley, Damian; Caulfield, Mark J.

doi:10.1016/j.jacadv.2023.100573

Cited by 9 publications

(3 citation statements)

References 33 publications

(57 reference statements)

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“…[24] Therefore, as a result, CYP2C19 gene polymorphism is considered an independent factor contributing to indi- vidual variations in clopidogrel treatment outcomes. [25] However, prior studies of genetic polymorphisms in CYP2C19 and their relationship with clinical efficacy have not included East Asian populations. [26] The frequency of CYP2C19 LoF alleles and the level of platelet reactivity differ between East Asians and Whites.…”

Section: Discussion Cyp2c19 Gene Impact On Platelet Functionmentioning

confidence: 99%

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

HU,

WANG,

FAN

et al. 2024

Journal of Geriatric Cardiology

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Objective To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with longterm 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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Section: Discussion Cyp2c19 Gene Impact On Platelet Functionmentioning

confidence: 99%

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

HU,

WANG,

FAN

et al. 2024

Journal of Geriatric Cardiology

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“…These phenotypes were created using previously described methods. 32 , 33 SNOMED codes, ICD codes and Office of Population Censuses and Surveys (OPCS) codes were obtained from linkage with electronic health records (including NHS digital, Barts Health NHS trust, Bradford teaching hospitals and primary care CCGs). 32 , 33 The first occurrence of diagnoses was identified using UK Biobank methods, with the addition of primary and secondary care SNOMED code data.…”

Section: Methodsmentioning

confidence: 99%

Factor V Leiden, estrogen, and multimorbidity association with venous thromboembolism in a British-South Asian cohort

Magavern,

Smedley,

Caulfield

2023

iScience

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“…Part of the reason for this is that cardiologists have moved on to the more potent anti-platelet agent ticagrelor, but even when clopidogrel is used -for example in elderly patients with a high risk of bleeding -genotyping is not performed or mentioned in clinical guidelines from the cardiology societies. It is also important to note that in Asian patients, where the frequency of the CYP2C19 polymorphism frequency is higher than in European patients, the lack of genotyping before the use of clopidogrel seems to have an even more dramatic impact on clinical outcomes [43].…”

Section: Clopidogrelmentioning

confidence: 99%

Precision medicine in cardiovascular therapeutics: Evaluating the role of pharmacogenetic analysis prior to drug treatment

Ingelman‐Sundberg,

Pirmohamed

2024

J Intern Med

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Pharmacogenomics is the examination of how genetic variation influences drug metabolism and response, in terms of both efficacy and safety. In cardiovascular disease, patient‐specific diplotypes determine phenotypes, thereby influencing the efficacy and safety of drug treatments, including statins, antiarrhythmics, anticoagulants and antiplatelets. Notably, polymorphisms in key genes, such as CYP2C9, CYP2C19, VKORC1 and SLCO1B1, significantly impact the outcomes of treatment with clopidogrel, warfarin and simvastatin. Furthermore, the CYP2C19 polymorphism influences the pharmacokinetics and safety of the novel hypertrophic cardiomyopathy inhibitor, mavacamten. In this review, we critically assess the clinical application of pharmacogenomics in cardiovascular disease and delineate present and future utilization of pharmacogenomics. This includes insights into identifying missing heritability, the integration of whole genome sequencing and the application of polygenic risk scores to enhance the precision of personalized drug therapy. Our discussion encompasses health economic analyses that underscore the cost benefits associated with pre‐emptive genotyping for warfarin and clopidogrel treatments, albeit acknowledging the need for further research in this area. In summary, we contend that cardiovascular pharmacogenomic analyses are underpinned by a wealth of evidence, and implementation is already occurring for some of these gene–drug pairs, but as with any area of medicine, we need to continually gather more information to optimize the use of pharmacogenomics in clinical practice.

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CYP2C19 Genotype Prevalence and Association With Recurrent Myocardial Infarction in British–South Asians Treated With Clopidogrel

Cited by 9 publications

References 33 publications

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

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

Factor V Leiden, estrogen, and multimorbidity association with venous thromboembolism in a British-South Asian cohort

Precision medicine in cardiovascular therapeutics: Evaluating the role of pharmacogenetic analysis prior to drug treatment

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