Clinical non-effectiveness of clopidogrel use for peripheral artery disease in patients with CYP2C19 polymorphisms: a systematic review

Huang, Shu; Yang, Seonkyeong; Ly, Shirly; Yoo, Ryan H.; Lo‐Ciganic, Wei‐Hsuan; Eadon, Michael T.; Schleyer, Titus; Whipple, Elizabeth C.; Nguyen, Khoa A.

doi:10.1007/s00228-022-03346-7

Cited by 7 publications

(5 citation statements)

References 39 publications

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“…A subsequent meta-analysis confirmed the greater risk of ischemic stroke among carriers [25]. Even more limited data are available for PAD, however a recent systematic review of small studies demonstrated worse outcomes for CYP2C19 LOF patients [26]. Finally, the multicenter, open-label RCT GENPAD (Genotype-guided Strategy for Antithrombotic Treatment in Peripheral Arterial Disease, (https://classic.clinicaltrials.gov/ct2/show/NCT04619927, accessed on 23 October 2023) is ongoing.…”

Section: Introductionmentioning

confidence: 91%

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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Section: Introductionmentioning

confidence: 91%

Pharmacogenomics of Cardiovascular Drugs for Atherothrombotic, Thromboembolic and Atherosclerotic Risk

Mauriello,

Ascrizzi,

Molinari

et al. 2023

Genes

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“…Pharmacogenetic data are more limited for patients receiving clopidogrel for PAD. A recent systematic review identified three observational studies evaluating CYP2C19 genotype effects on outcomes in clopidogrel‐treated patients with PAD; sample sizes ranged from 50 to 278 patients 82 . Two studies assessed restenosis or occlusion following an endovascular procedure, and the third assessed amputation and death.…”

Section: Pharmacogenetic Data With Clopidogrel For Peripheral Artery ...mentioning

confidence: 99%

Pharmacogenetics ofP2Y₁₂receptor inhibitors

et al. 2023

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Oral P2Y12 inhibitors are commonly prescribed for cardiovascular disease and include clopidogrel, prasugrel, and ticagrelor. Each of these drugs has its strengths and weaknesses. Prasugrel and ticagrelor are more potent inhibitors of platelet aggregation and were shown to be superior to clopidogrel in preventing major adverse cardiovascular events after an acute coronary syndrome and percutaneous coronary intervention (PCI) in the absence of genotyping. However, both are associated with an increased risk for non‐coronary artery bypass‐related bleeding. Clopidogrel is a prodrug requiring bioactivation, primarily via the CYP2C19 enzyme. Approximately 30% of individuals have a CYP2C19 no function allele and decreased or no CYP2C19 enzyme activity. Clopidogrel‐treated carriers of a CYP2C19 no function allele have decreased exposure to the clopidogrel active metabolite and lesser inhibition of platelet aggregation, which likely contributed to reduced clopidogrel efficacy in clinical trials. The pharmacogenetic data for clopidogrel are most robust in the setting of PCI, but evidence is accumulating for other indications. Guidance is available from expert consensus groups and regulatory agencies to assist with integrating genetic information into P2Y12 inhibitor prescribing decisions, and CYP2C19 genotype‐guided antiplatelet therapy after PCI is one of the most common examples of clinical pharmacogenetic implementation. Herein, we review the evidence for pharmacogenetic associations with clopidogrel response and outcomes with genotype‐guided P2Y12 inhibitor selection and describe guidance to assist with pharmacogenetic implementation. We also describe processes for applying genotype data for P2Y12 inhibitor therapy selection and remaining gaps in the field. Ultimately, consideration of both clinical and genetic factors may guide selection of P2Y12 inhibitor therapy that optimally balances the atherothrombotic and bleeding risks.

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“…Research studies in both cardiac and stroke medicine have demonstrated significantly worse outcomes in patients treated with clopidogrel who are poor metabolisers of CYP2C19, and major guidelines have advocated a role of genetic testing in these specialties [5][6][7] . Research into the impact of CYP2C19 alleles in vascular surgery is much more limited, but does suggest an association between poor metabolisers of CYP2C19 and adverse outcomes in patients taking clopidogrel 8 . This protocol describes a prospective observational cross-sectional study which aims to establish the relationship between patient genotype and outcomes after revascularisation in patients with CLTI who are prescribed clopidogrel.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Prospective Observational Study to Assess the Impact of Pharmacogenetics on Outcomes in Vascular Surgery (PROSPER)

Burke,

Mirza,

Wright

et al. 2024

Preprint

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IntroductionPatients with chronic limb threatening ischaemia (CLTI) are often prescribed clopidogrel in order to reduce their risk of major adverse limb and cardiovascular events. Clopidogrel is metabolised by the CYP2C19 enzyme, and genetics variations inCYP2C19are common. These variants can influence an individual’s ability to metabolise clopidogrel to its active metabolite. This work aims to establish the relationship between patient genotype and outcomes after revascularisation in patients with CLTI who are prescribed clopidogrel. It will consider whether pharmacogenetics can be used to ensure patients are prescribed effective medications to optimise their outcomes.Methods and analysisThis is a prospective observational cross-sectional study of patients undergoing lower limb surgical, endovascular or hybrid revascularisation for CLTI. Patients taking clopidogrel post-procedure, as well as those prescribed a non-clopidogrel based medication regimen, will be recruited prior to or shortly after revascularisation. Patients will undergoCYP2C19genotyping and will be followed-up using online records.Ethics and disseminationManchester University Research Ethics Committee approval as obtained was part of the Implementing Pharmacogenetics to Improve Prescribing (IPTIP) trial process (IRAS 305751). The results of the study will be published in a peer-review journal and presented at international conferences.RegistrationThis work is a sub-protocol for the IPTIP study which is registered asISRCTN14050335.

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Clinical non-effectiveness of clopidogrel use for peripheral artery disease in patients with CYP2C19 polymorphisms: a systematic review

Cited by 7 publications

References 39 publications

Pharmacogenomics of Cardiovascular Drugs for Atherothrombotic, Thromboembolic and Atherosclerotic Risk

Pharmacogenomics of Cardiovascular Drugs for Atherothrombotic, Thromboembolic and Atherosclerotic Risk

Pharmacogenetics ofP2Y₁₂receptor inhibitors

A Prospective Observational Study to Assess the Impact of Pharmacogenetics on Outcomes in Vascular Surgery (PROSPER)

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Clinical non-effectiveness of clopidogrel use for peripheral artery disease in patients with CYP2C19 polymorphisms: a systematic review

Cited by 7 publications

References 39 publications

Pharmacogenomics of Cardiovascular Drugs for Atherothrombotic, Thromboembolic and Atherosclerotic Risk

Pharmacogenomics of Cardiovascular Drugs for Atherothrombotic, Thromboembolic and Atherosclerotic Risk

Pharmacogenetics ofP2Y12receptor inhibitors

A Prospective Observational Study to Assess the Impact of Pharmacogenetics on Outcomes in Vascular Surgery (PROSPER)

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Product

Resources

About

Pharmacogenetics ofP2Y₁₂receptor inhibitors