Key result
CYP2C19 genotype-guided therapy reduces MACE by switching loss-of-function carriers from clopidogrel to alternative agents.
Why the study?
CYP2C19 loss-of-function alleles alter clopidogrel outcomes and increase risks after percutaneous coronary intervention, prompting an exploration of the successes and challenges of advancing CYP2C19 genotyping into routine clinical care.
Does CYP2C19 genotype-guided antiplatelet therapy improve outcomes in patients taking clopidogrel following percutaneous coronary intervention?
Does CYP2C19 genotype-guided antiplatelet therapy improve outcomes in patients taking clopidogrel following percutaneous coronary intervention?
CYP2C19 genotyping has the potential to guide antiplatelet therapy in patients undergoing PCI, given the association of loss-of-function alleles with adverse cardiovascular events on clopidogrel.
May support genotype-guided switching post-PCI; leaves open confirmation in prospective randomized trials.
Pharmacogenetic variants can alter the mechanism of action (pharmacodynamic gene variants) or kinetic processes such as absorption, distribution, metabolism and elimination (pharmacokinetic gene variants). Many initial successes in precision medicine occurred in the context of genes encoding the cytochromes P450 (CYP enzymes). CYP2C19 activates the antiplatelet drug clopidogrel, and polymorphisms in the CYP2C19 gene are known to alter the outcome for patients taking clopidogrel in the context of cardiovascular disease. CYP2C19 loss-of-function alleles are specifically associated with increased risk for coronary stent thrombosis and major adverse cardiovascular events in patients taking clopidogrel following percutaneous coronary intervention. We explore successes and challenges encountered as the clinical and scientific communities advance CYP2C19 genotyping in the context of routine patient care.
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Ellithi et al. (2020) conducted a review in Cardiovascular disease. CYP2C19 genotype-guided antiplatelet therapy vs. Conventional antiplatelet therapy was evaluated. CYP2C19 genotype-guided antiplatelet therapy reduces the risk of major adverse cardiovascular events by identifying patients with loss-of-function alleles who benefit from switching from clopidogrel to alternative agents.