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Published on: April 1, 2019
Role of genetic polymorphisms in clopidogrel response variability: a systematic review
Jose Lopez1, Justin Mark2, Gustavo J Duarte3
1Division of Cardiovascular Disease, University of Miami Miller School of Medicine, Lantana, Florida, USA jll296@med.miami.edu.
Insights
Genetic variations in CYP2C19 affect clopidogrel metabolism, leading to treatment resistance in up to 30% of patients. Genotyping before therapy can guide personalized treatment to prevent adverse cardiovascular events.
Area of Science:
- Pharmacogenomics
- Cardiovascular Medicine
- Clinical Chemistry
Background:
- Clopidogrel, a P2Y12 inhibitor, is crucial post-percutaneous coronary intervention with drug-eluting stents.
- It prevents restenosis, sudden cardiac death, and ischemic strokes in patients with vascular disease.
- However, its efficacy is compromised by CYP2C19 genetic polymorphisms, leading to inadequate response in up to 30% of patients.
Approach:
- Investigated worldwide prevalence of CYP2C19 genetic polymorphisms affecting clopidogrel metabolism.
- Reviewed the clinical utility of personalized CYP2C19 genotyping.
- Aimed to mitigate treatment resistance and associated patient burden.
Key Points:
- CYP2C19 genotype significantly influences clopidogrel prodrug metabolism and patient response.
- Allelic frequencies of CYP2C19 variants show ethnic and geographic similarities.
- Personalized CYP2C19 genotyping can identify patients at risk for clopidogrel non-response.
Conclusions:
- Genotyping before clopidogrel initiation is recommended to guide personalized therapy.
- This approach can optimize dosage or suggest alternative P2Y12 inhibitors.
- Precision medicine strategies, including CYP2C19 genotyping, are vital to prevent treatment failure and adverse events in patients with genetic variants.
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.
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