Clopidogrel (Plavix) is a pro-drug, meaning that after being taken orally it must be metabolized to its active, platelet-inhibiting form 2-oxo-clopidogrel, in the liver. The protein in the liver responsible for this activation is the cytochrome p450 enzyme CYP2C19 (pronounced "sip two see nineteen").

Across populations, CYP2C19 protein alleles can have different genetic variants that impact its ability to activate clopidogrel. The different alleles can produce five different metabolism phenotypes: ultrarapid, rapid, normal, intermediate and poor metabolism. Of these, the intermediate and poor metabolism phenotypes have been shown to increase the risk of inadequate platelet response and may result in adverse cardiovascular and cerebrovascular events in individuals prescribed clopidogrel.

The Clinical Pharmacogenetics Implementation Consortium (CPIC) is a group who evaluates the evidence for the use of pharmacogenetics and then develops clinical practice guidelines.  For clopidogrel, extensive guideline information can be found at: https://cpicpgx.org/guidelines/guideline-for-clopidogrel-and-cyp2c19/ a reference maintained by CPIC. 

Here is a video that reviews the CPIC guideline for clopidogrel: https://www.youtube.com/watch?v=qxzsy-2KF3s 

The US FDA issued a black box warning for clopidogrel in 2010: https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fda-drug-safety-communication-reduced-effectiveness-plavix-clopidogrel-patients-who-are-poor 

At UCHealth the use of pharmacogenetics when prescribing clopidogrel will occur in patients who meet the following conditions:

1) Provided a blood or saliva sample to the CCPM biobank, consented for the return of their results, and this sample has undergone genotyping OR the patient is being seen in a clinic which is currently using pharmacogenetic testing as part of standard care (e.g., the UCHealth GI Oncology Clinic).  
2) Are prescribed clopidogrel.  

This process takes a minimum of 4-6 weeks, but may take several years. Therefore, results will not be available at initial presentation if a patient has not previously enrolled in the biobank.

If you are a provider AND your patient is a CYP2C19 intermediate or poor metabolizer, a best practice alert (BPA) will warn you if you attempt to prescribe clopidogrel in UCHealth's EHR.  This BPA will fire in both the inpatient and ambulatory settings in the UCHealth EHR only. The BPA prompts the selection of an alternate antiplatelet agent.  There is patient education text available for UCHealth providers to use in discharge paperwork or the after visit summary (AVS).