Background
Following publication of NICE diagnostic guidance 59 – CYP2C19 genotype testing to guide clopidogrel use after ischaemic stroke or transient ischaemic attack, NHS England are delivering a national pilot to produce an implementation guide for providers and information to support future commissioning decisions. St George’s Hospital is one of four sites for the pilot which will run until summer 2025. This applies only to new patients who are part of the pilot, not those already prescribed clopidogrel.
CYP2C19 metabolises clopidogrel, a pro-drug, to its active form. Due to variations in the gene, people may be classified as poor, intermediate, normal, rapid or ultra-rapid metabolisers. Poor or intermediate metabolisers of CYP2C19 are less likely to receive a therapeutic benefit from clopidogrel due to reduced exposure to the active metabolite and are recommended to use alternative antiplatelet therapy; they may be considered ‘clopidogrel resistant’. Normal, rapid and ultra-rapid metabolisers can be treated with clopidogrel.
Antiplatelet drug choice and dosing recommendations
This guidance takes into consideration consensus-based recommendations from the Clinical Pharmacogenetic Implementation Consortium (CPIC), National Clinical Guideline for Stroke 2023, THALES study and the SOCRATES study
- This only applies to adult patients with acute stroke requiring antiplatelet therapy with clopidogrel. It does not apply to patients with haemorrhagic stroke, those who require anticoagulation (e.g. for atrial fibrillation) or for patients who are not presenting with a new stroke. Clopidogrel will only be prescribed once it is known that a patient is a normal, rapid or ultra-rapid metaboliser.
- Patients appropriate for single antiplatelet therapy (presenting to St George’s Hyper Acute Stroke Unit) will be prescribed aspirin 300mg loading once only then 75mg once daily until the CYP2C19 genotype result is available.
- Patients appropriate for dual antiplatelet therapy will be prescribed the THALES regimen as appropriate: ticagrelor 180mg loading for one dose then 90mg twice daily co-administered with aspirin 75mg once daily for 30 days. Following this, they should be prescribed clopidogrel 75mg once daily unless the CYP2C19 result shows they are poor or intermediate CYP2C19 metabolisers.
- For patients who are poor or intermediate CYP2C19 metabolisers, the antiplatelet of choice is aspirin.
- For patients who are clopidogrel poor or intermediate CYP2C19 metabolisers and aspirin intolerant, the antiplatelet of choice is ticagrelor (90mg twice daily long-term).
- Please note: although included in the BNF and National Clinical Guideline for Stroke, these recommendations fall outside ticagrelor’s Summary of Products Characteristics.
Aspirin intolerance – Patients who either demonstrate a hypersensitivity reaction to aspirin or experience side effects that make continuance of the aspirin ill advised.
Primary Care
- Most patients will be initiated on ticagrelor whilst an inpatient and provided with a 4-week supply from secondary care.
- If a patient is discharged prior to CYP2C19 result, a secondary care clinician will contact both the patient and GP surgery with the result and subsequent antiplatelet plan:
- If the result comes back as normal/rapid/ultra-rapid CYP2C19 metaboliser, change aspirin to clopidogrel 75mg daily long-term at next prescription request
- If the result comes back as poor or intermediate CYP2C19 metaboliser, the patient will remain on aspirin 75mg daily long-term
- Stroke patients have a 3-month outpatient review with a stroke specialist
Coding recommendations for primary care
Code the patient’s metaboliser status in their medical record as far as possible and be aware that current electronic prescribing systems do not flag drug-gene interactions.
There is currently no NHS guideline or national standard on how records should be maintained around pharmacogenomic testing. However, until a national approach to this topic is agreed, local service providers may wish to use existing SNOMED-CT terms to annotate CYP2C19 pharmacogenomic results in the patient record. These include the following codes, in descending order of CYP2C19 activity:
- Cytochrome P450 family 2 subfamily C member 19 ultra-rapid metaboliser (finding) SCTID: 738790007
- Cytochrome P450 family 2 subfamily C member 19 rapid metaboliser (finding) SCTID: 787193001
- Cytochrome P450 family 2 subfamily C member 19 normal metaboliser (finding) SCTID: 738788006
- Cytochrome P450 family 2 subfamily C member 19 intermediate metaboliser (finding) SCTID: 738787001
- Cytochrome P450 family 2 subfamily C member 19 poor metaboliser (finding) SCTID: 738786005
Further advice and guidance
If further advice or guidance is required, consult pharmacy or refer to the St George’s clinical pharmacology clinic. For internal referrals use PowerChart orders (‘Refer to Clinical Pharmacology/Polypharmacy’); for external referrals use NHS e-referral service (e-RS) (‘Clinical Pharmacology & Polypharmacy’ in the General Medicine filter). In an emergency, GPs can call St George’s and ask to speak to the stroke registrar on-call.
References/resources
National Genomics Education Programme. GeNotes. Clopidogrel Knowledge Hub. July 2023
British National Formulary (BNF). Ticagrelor
V1.0 Approved by Integrated Medicines Optimisation Committee (IMOC) June 2025