Key result
The CYP2C19*2 loss-of-function polymorphism is associated with decreased metabolisation of clopidogrel, poor antiplatelet effect, and an increased risk of major adverse cardiovascular events including stent thrombosis.
Why the study?
Does the presence of CYP2C19*2 loss-of-function polymorphism increase major adverse cardiovascular events including stent thrombosis in high risk vascular patients on clopidogrel treatment?
Does the presence of CYP2C19*2 loss-of-function polymorphism increase major adverse cardiovascular events including stent thrombosis in high risk vascular patients on clopidogrel treatment?
The CYP2C19*2 loss-of-function polymorphism significantly impairs clopidogrel metabolism, leading to high on-treatment platelet reactivity and an increased risk of major adverse cardiovascular events such as stent thrombosis.
Highlights CYP2C19*2-related clopidogrel resistance and MACE risk; leaves open whether testing improves outcomes.
IMPORTANCE OF THE FIELD: Major adverse cardiovascular events including stent thrombosis associated with residual platelet reactivity on antiplatelet treatment in high risk vascular patients is a hot issue that needs a strong effort to be solved. Dual antiplatelet therapy with clopidogrel and aspirin prevents ischemic events and improves outcomes following acute coronary syndromes and percutaneous coronary intervention. However, adverse cardiovascular events occur in these patients, and several studies have shown that patients who suffer cardiovascular complications have high post-treatment platelet reactivity despite antiplatelet treatment. Clopidogrel requires conversion to active metabolite by CYP isoenzymes. Recently, CYP2C19*2 polymorphism (G681A nucleotide substitution) has been shown to be associated with decreased metabolisation of clopidogrel, poor antiaggregant effect and increased adverse cardiovascular events. AREAS COVERED IN THIS REVIEW: This review summarises the principal studies contributing to establish the relationship between CYP2C19*2 polymorphism and adverse outcomes in high risk patients on clopidogrel treatment. TAKE HOME MESSAGE: Prospective studies are urgently needed to determine the clinical impact of a score that takes into account individual characteristics of patients - CYP2C19*2 genotypes, residual platelet reactivity, drug-drug interaction, as well as traditional and procedural risk factors - for the identification of the therapeutic strategy that provides the best benefit for the single subject.
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Giusti et al. (2010) conducted a review in High-risk vascular patients undergoing percutaneous coronary intervention with stent implantation. CYP2C19*2 loss-of-function polymorphism vs. CYP2C19 wild-type / noncarriers was evaluated on Major adverse cardiovascular events and stent thrombosis. The CYP2C19*2 loss-of-function polymorphism is associated with decreased metabolisation of clopidogrel, poor antiplatelet effect, and an increased risk of major adverse cardiovascular events including stent thrombosis.
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