Updated recommendations for CYP2C19 genotyping with clopidogrel
MedWire News: A US review provides guidance on the appropriate use of pharmacogenomic testing for the CYP2C19 genotype and subsequent clopidogrel therapy.
Clinicians can consider genotyping high-risk acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI) patients, such as those who have had a previous cardiovascular event, or those with multivessel coronary disease, say experts.
The updated review and recommendations are published in the journal of Clinical and Pharmacological Therapeutics by Alan Shuldiner (University of Maryland, Baltimore) and colleagues.
The hepatic CYP2C19 enzyme is involved in the metabolism of numerous drugs, including clopidogrel, but various genetic alleles are known to impair drug metabolism.
The most common CYP2C19 loss-of-function allele occurs in approximately 15% of Caucasians and 30% of Asians.
This allele, CYP2C19*2, is associated with an increased risk for adverse cardiovascular events in homozygous and heterozygous ACS patients treated with clopidogrel.
As a result of the growing evidence linking CYP2C19*2 to adverse clinical outcomes, the US Food and Drug Administration (FDA) implemented a black-box warning for clopidogrel.
In their review, the researchers, part of the Clinical Pharmacogenetics Implementation Consortium (CPIC), note that clinical genotyping tests are available, but only the CYP2C19*2 allele has been adequately studied with respect to clinical outcomes with clopidogrel.
They suggest that other antiplatelet agents, such as prasugrel, be used in patients considered to be intermediate metabolizers of CYP2C19 based on genotype.
In patients considered poor metabolizers - ie, those homozygous for CYP2C19*2 - the group strongly recommends that clinicians use prasugrel or other antiplatelet agents.
While some pilot studies have shown increasing the maintenance dose of clopidogrel to 150 mg/day in poor responders is beneficial, Shuldiner and colleagues say it is premature to make such a recommendation.
The group notes that in the absence of clinical trial data, there is some risk to switching a patient's therapy on the basis of their CYP2C19 genotype.
The American College of Cardiology and the American Heart Association do not recommend genetic testing, mainly because there are no clinical trials of genotype-directed antiplatelet therapy.
One of the future challenges will be for the rapid turnaround of genetic test results. It would be helpful to clinicians to have access to the genetic information before therapy is started, according to the review.
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