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Will your patients receive the full benefits of clopidogrel?
PLAVIXTM (the brand name for clopidogrel) is the world's second best-selling drug. Patients with certain genetic variants may not receive the full benefit of clopidogrel. They poorly metabolize the drug into an active form and are therefore at an increased risk of thrombosis. The Food and Drug Administration estimates that between 2-14% of the US population are poor metabolizers of clopidogrel.
Know before you prescribe with our Clopidogrel GenoSTAT test
Our Clopidogrel GenoSTAT test is an easy-to-administer test that determines an individual's ability to activate the drug copidogrel. It reports if they are a poor, intermediate or extensive metabolizer.
Variants in the CYP2C19 gene cause the liver enzyme that converts PLAVIXTM to its active form to be less effective. The Iverson Clopidogrel GenoSTAT will clearly report your patients CYPC19 variant(s),*2 or *3, and metabolizer type.
Iverson's reports are developed with the medical professional in mind. Should you have questions about our reports or need more detailed information regarding results, please contact us for direct service.
Who should be tested?
Our Clopidogrel GenoSTAT test will determine drug effectiveness before prescription, in comparison to other clopidogrel testing methods that require the patient be on the drug for 7-10 days.
Individuals for whom clopidogrel may be prescribed as a treatment for the following conditions:
- Stent placement
- Thromboembolic diseases/events
- Pulmonary embolism
- Myocardial infarction
- Peripheral artery disease
- Stroke
- Thromboembolic events
- Myocardial infraction
- Atrial fibrillation
- Other determine prescribing reasons
Testing Specifics and Incidence
Iverson's Clopidogrel GenoSTAT test identifies the genetic (CYP2C19) cause of an individual's PLAVIXTM resistance, detects mutation of the P450-2C19 genotypes (*2, *3, *4, *5, *6, *7 ,* 8 & *17) and determines if a patient should be prescribed clopidogrel as a therapy. The test offers 8 different variants.
In CYP2C19 variants, *1 is considered to be the normal or "wild" type. *2 and *3 are commonly identified variants and cause reduced levels of active (functional) clopidogrel. Mutations in *2 and *3 account for 95% of genetic variants in the CYP2C19 gene for the population as a whole.
The CYP2C19 gene and associated variant forms determine the level of functional CYP2C19 enzymes in the liver responsible for converting clopidogrel to an active drug. Liver enzymes, coded by the CYP2C19 genes, convert the inactive "prodrug" clopidogrel into its physiological active form. A patient is classified as an extensive (normal) drug metabolizer, intermediate drug metabolizer, poor drug metabolizer or in some cases ultra-rapid drug metabolizer. Significant differences exist in the frequency of CYP2C19 gene variants among sub-populations.
A Surprising New Variant: The *17 Gain-of-Function "Ultra-Rapid Metabolizer"
A new CYP2C19 gene mutation, the *17 variant, will add yet more complexity to the evaluation of clopidogrel therapy. The *17 variant is unique in that it results in an enzyme that is classified as gain-of-function, and the patient is considered an ultra-rapid metabolizer. Dr. Sibbing and associates reported in the February 2010 issue of Circulation that, in 1,524 patients undergoing coronary stent placement, a single *17 gene variant resulted in about a 2-fold increase in the incidence in bleeding within 30 days following stent placement. The incidence of bleeding was 2.5% in patients without *17, but 4% in patients with a single *17 variant. Patients with the double *17/*17 genotype exhibited a dose-response 4-fold increase in bleeding (8%). The most striking finding was that out of the 1,524 patients tested, 35% had the single *17 variant and another 5% had the *17/*17 genotype. Reference (Sibbing, et al. Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement, Circulation, 2010, 121, 512-518.)
Recent Recommendations for Clinical Practice
1_In the recent recommendation from the American College of Cardiology on genotyping for clopidogrel it was suggested that for "moderate to high risk patients" genotyping may be considered to identify poor metabolizers. The ACC suggested this made sense, since as pointed out by the FDA, alternate therapies are available. (ACCF/AHA Clopidogrel Clinical Alert: Approaches to the FDA "Boxed Warning", David R. Holmes, Jr, et al. J. Am. Coll. Cardiol. published online Jun 28, 2010).
2_In apparent agreement with the ACC recommendation, researchers from the Scripps Institute have recently pointed out that with stent thrombosis rates in carriers of CYP2C19 as high as 11%, mortality associated with such events close to 50%, and a near 2-fold increase in the risk of bleeding in CYP2C19*17 carriers, that rather than wait years for results from future prospective trials to be initiated, it makes clinical sense to implement all potential interventions to help prevent the catastrophic outcomes of stent thrombosis and death in the tens of thousands of patients currently at risk. (The Case for Routine Genotyping in Dual-Antiplatelet Therapy. Samir B. Damani, and Eric J. Topol. J. Am. Coll. Cardiol. published online May 12, 2010)
PlavixTM is a registered trade name owned by Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership. There is no affiliation, sponsorship or endorsement by Bristol-Myers Squibb/Sanofi-Aventis Pharmaceuticals and Iverson Genetic Diagnostics, Inc.
References
1.
Annu Rev Pharmacol Toxicol 2001; 41: 815-50
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Iverson's Lab Requisition form (pdf)
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