CLOPIDOGREL A second-generation thienopyridine antiplatelet agent, an - - PowerPoint PPT Presentation

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Phe

henGen ene

P2Y12

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CLOPIDOGREL

• A second-generation thienopyridine antiplatelet agent, an antagonist of platelet P2Y12 receptor
• Inhibits the formation of blood clots in the coronary, peripheral & cerebrovascular arteries

METABOLISM AND ACTION OF CLOPIDOGREL

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Pharmacodynamic evidence recognized by the FDA, American College of Cardiology, American Heart Association, and European Society of Cardiology suggests that clopidogrel has a suboptimal effect in a substantial proportion (“about one third”) of patients and that increasing the dose has limited efficacy in selected patients.

Problem – limited effectiveness of clopidogrel

Clopidogrel is not effective in about 1/3 of individuals One of the most prevalent reasons for reduced response to CLOPIDOGREL is inefficient conversion of the drug into its active metabolite due to genetic variability in liver enzymes

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Clopidogrel effectiveness is not routinely measured due to

• current assessment of platelet function requiring testing within a

limited time of taking the blood sample

• specialised equipment and technical expertise requirements on site

No easy-to-use test for clopidogrel effectiveness

• Ineffective treatment can increase the risk of a recurrent cardiac

event or stroke

• Overly effective treatment can lead to excessive bleeding

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Our Solution

To identify patients who are not responding to Clopidogrel using Phe henGen ene P2Y12

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Test that includes:

• Genotyping: CYP2C19 enzyme
• Involved in the metabolism of clopidogrel
• Every individual has two CYP2C19 alleles
• Depending on the combination of alleles in an individual, drug-

metabolizing phenotypes associated with the CYP2C19 enzyme can vary

• Phenotyping: assessing platelet reactivity in response to stimulation with

agonists

• High
• n-treatment

platelet reactivity correlates with recurrent thrombotic events Blood samples are collected, processed using simple kit and are sent for analysis at a central laboratory – no need for specialised equipment on site and no time limitations to perform the analysis

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Supporting Studies

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Importance of CYP2C19 Genotyping

In 2009, the US Food and Drug Administration (FDA) issued a boxed warning, recommending “consideration

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CYP2C19 genotype” prior to prescribing clopidogrel.

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Assess anywhere

Patient on antiplatelet therapy can be assessed in primary care or home setting

Sample Collection & Processing

Blood sample taken and processed using simple, drug-specific kit

Sample Shipment

Processed sample is shipped to a central processing lab in the UK

Sample analysed

Laboratory staff analyse sample for P-selectin using flow cytometry and CYP2C19 using Luminex Platform

Electronic reporting

Complete test results are reported back electronically

OUR WORKFLOW

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Advantages of this combined testing

• Identify at risk patients with sub-optimal response to Clopidogrel

using both genotyping and phenotyping approaches

• Results allow healthcare providers tailor the prescription of

antiplatelet agents for their patients accordingly to reduce the risk of myocardial infarction, stent thrombosis or stroke

• No capital investment is required on site to setup the testing – all

that is needed is an easy-to-use testing kit to process and stabilise the blood sample, which is then sent for expert analysis to a central laboratory