Role of genetic polymorphisms in clopidogrel response variability: a systematic review
Introduction Clopidogrel is a P2Y12 inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its potential complications, including sudden cardiac death and ischaemic strokes in patients with significant vascular...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2023-11-01
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| Series: | Open Heart |
| Online Access: | https://openheart.bmj.com/content/10/2/e002436.full |
| _version_ | 1827391368653176832 |
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| author | José López An Tran Justin Mark Gustavo J Duarte Mohammed Shaban Franklin Sosa Rishabh Mishra Swati Jain Asma Khizar Daniel Karpel Giancarlo Acosta Miguel Rodriguez-Guerra |
| author_facet | José López An Tran Justin Mark Gustavo J Duarte Mohammed Shaban Franklin Sosa Rishabh Mishra Swati Jain Asma Khizar Daniel Karpel Giancarlo Acosta Miguel Rodriguez-Guerra |
| author_sort | José López |
| collection | DOAJ |
| description | Introduction Clopidogrel is a P2Y12 inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its potential complications, including sudden cardiac death and ischaemic strokes in patients with significant vascular disease.Areas covered As a prodrug, the metabolism and efficacy of clopidogrel are contingent on the presence of wild-type CYP450 (CYP2C19) alleles. Genetic polymorphisms and variants are well known to impair its ability to prevent major adverse cardiovascular events in these patients, with inadequate response rates as high as 30% in previous publications. Patterns of allelic frequencies are expected to exhibit similarities between individuals of the same ancestry, ethnic group or geographic region. Accordingly, we seek to further elucidate worldwide prevalence rates for genetic polymorphisms in the CYP2C19-dependent metabolism of clopidogrel and review the potential of personalised CYP2C19 genotyping in clinical practice to mitigate this high treatment resistance and its associated burden on patients.Experts’ commentary Our findings support the consideration of genotyping before initiation of therapy to guide adequate dosage or substitutions of other P2Y12 inhibitors to promote personalised, precision medicine and to prevent adverse events when these therapies may inevitably fail in patients with variants of the CYP450 (CYP2C19) system. |
| first_indexed | 2024-03-08T17:09:53Z |
| format | Article |
| id | doaj.art-8841cae4342142cea354fd8067ccb62c |
| institution | Directory Open Access Journal |
| issn | 2053-3624 |
| language | English |
| last_indexed | 2024-03-08T17:09:53Z |
| publishDate | 2023-11-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Open Heart |
| spelling | doaj.art-8841cae4342142cea354fd8067ccb62c2024-01-03T22:15:07ZengBMJ Publishing GroupOpen Heart2053-36242023-11-0110210.1136/openhrt-2023-002436Role of genetic polymorphisms in clopidogrel response variability: a systematic reviewJosé López0An Tran1Justin Mark2Gustavo J Duarte3Mohammed Shaban4Franklin Sosa5Rishabh Mishra6Swati Jain7Asma Khizar8Daniel Karpel9Giancarlo Acosta10Miguel Rodriguez-Guerra11Division of Cardiovascular Disease, University of Miami Miller School of Medicine, Lantana, Florida, USADepartment of Internal Medicine, Montefiore Health System, Albert Einstein College of Medicine, Bronx, New York, USADepartment of Internal Medicine, University of Miami Miller School of Medicine, Fort Lauderdale, Florida, USADivision of Cardiology, Cleveland Clinic Florida, Weston, Florida, USADepartment of Internal Medicine, BronxCare Health System, Icahn School of Medicine at Mount Sinai, New York, New York, USADepartment of Internal Medicine, BronxCare Health System, Icahn School of Medicine at Mount Sinai, New York, New York, USADepartment of Internal Medicine, Montefiore Health System, Albert Einstein College of Medicine, Bronx, New York, USADepartment of Internal Medicine, Montefiore Health System, Albert Einstein College of Medicine, Bronx, New York, USADepartment of Internal Medicine, Montefiore Health System, Albert Einstein College of Medicine, Bronx, New York, USADepartment of Internal Medicine, HCA Florida Aventura Hospital and Medical Center, Aventura, Florida, USADivision of Cardiology, Georgia Heart Institute, Gainesville, Florida, USADepartment of Internal Medicine, Montefiore Health System, Albert Einstein College of Medicine, Bronx, New York, USAIntroduction Clopidogrel is a P2Y12 inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its potential complications, including sudden cardiac death and ischaemic strokes in patients with significant vascular disease.Areas covered As a prodrug, the metabolism and efficacy of clopidogrel are contingent on the presence of wild-type CYP450 (CYP2C19) alleles. Genetic polymorphisms and variants are well known to impair its ability to prevent major adverse cardiovascular events in these patients, with inadequate response rates as high as 30% in previous publications. Patterns of allelic frequencies are expected to exhibit similarities between individuals of the same ancestry, ethnic group or geographic region. Accordingly, we seek to further elucidate worldwide prevalence rates for genetic polymorphisms in the CYP2C19-dependent metabolism of clopidogrel and review the potential of personalised CYP2C19 genotyping in clinical practice to mitigate this high treatment resistance and its associated burden on patients.Experts’ commentary Our findings support the consideration of genotyping before initiation of therapy to guide adequate dosage or substitutions of other P2Y12 inhibitors to promote personalised, precision medicine and to prevent adverse events when these therapies may inevitably fail in patients with variants of the CYP450 (CYP2C19) system.https://openheart.bmj.com/content/10/2/e002436.full |
| spellingShingle | José López An Tran Justin Mark Gustavo J Duarte Mohammed Shaban Franklin Sosa Rishabh Mishra Swati Jain Asma Khizar Daniel Karpel Giancarlo Acosta Miguel Rodriguez-Guerra Role of genetic polymorphisms in clopidogrel response variability: a systematic review Open Heart |
| title | Role of genetic polymorphisms in clopidogrel response variability: a systematic review |
| title_full | Role of genetic polymorphisms in clopidogrel response variability: a systematic review |
| title_fullStr | Role of genetic polymorphisms in clopidogrel response variability: a systematic review |
| title_full_unstemmed | Role of genetic polymorphisms in clopidogrel response variability: a systematic review |
| title_short | Role of genetic polymorphisms in clopidogrel response variability: a systematic review |
| title_sort | role of genetic polymorphisms in clopidogrel response variability a systematic review |
| url | https://openheart.bmj.com/content/10/2/e002436.full |
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