Key result
CYP2C19 polymorphisms are linked to clopidogrel resistance and higher MACE risk across diverse populations.
Why the study?
Genetic variants in CYP2C19 impair clopidogrel efficacy with high inadequate response rates, prompting an evaluation of worldwide polymorphism prevalence and the potential for personalized CYP2C19 genotyping.
Does the presence of CYP2C19 genetic polymorphisms alter the clinical efficacy of clopidogrel and increase the risk of major adverse cardiovascular events in adult patients?
Systematic Review
Does the presence of CYP2C19 genetic polymorphisms alter the clinical efficacy of clopidogrel and increase the risk of major adverse cardiovascular events in adult patients?
Due to persistently high worldwide rates of CYP2C19 genetic polymorphisms that significantly impair clopidogrel efficacy, personalized genetic testing may be warranted to guide antiplatelet therapy and prevent ischemic events.
Reinforces CYP2C19-clopidogrel interaction consensus; leaves open optimal testing strategies in diverse populations.
INTRODUCTION: 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: 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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López et al. (2023) conducted a systematic review in Patients on clopidogrel therapy following percutaneous coronary intervention or for acute coronary syndrome. CYP2C19 genetic polymorphisms vs. Wild-type CYP2C19 alleles (normal metabolizers) was evaluated on Clopidogrel response variability and major adverse cardiovascular events (MACE). CYP2C19 genetic polymorphisms are persistently prevalent across various ethnic groups worldwide and are associated with clopidogrel resistance and an increased risk of major adverse cardiovascular events.
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