Early results from the CYP2C19 genotype testing pilot – a landmark moment for personalised stroke care

Following the successful completion of the NHS national pilot in April 2025, the highly anticipated first results assessing CYP2C19 genetic testing to guide clopidogrel use in ischaemic stroke and TIA patients have now been unveiled. These crucial clinical data serve as the foundation for the newly released NHS Implementation Guide for CYP2C19 testing which sets out practical considerations for integrating this pharmacogenomic test into clinical pathways and aligns with existing HealthTech guidance 724.  

Whilst NICE recommends CYP2C19 genetic testing, it also recognises that the test is not yet routinely commissioned or implemented in clinical care. The national pilot was therefore undertaken to test the feasibility of different testing approaches, including laboratory based and point of care testing, across multiple NHS sites. The findings from the pilot are now helping shape practical implementation guidance.

At PHG Foundation, we have been following this closely. Although the NHS has previously implemented PGx testing for focused use cases such as DPYD testing in oncology and the MT-RNR1 test in neonatal acute care, CYP2C19 genetic testing represents something fundamentally different. It is the first NICE-recommended pharmacogenomics test for a common condition, with tens of thousands of patients affected each year. If routinely implemented, this brings PGx firmly into mainstream cardiovascular medicine and raises system-wide questions about data sharing, commissioning, clinical decision support, and workforce readiness. 

What is CYP2C19 genetic testing and why does it matter in stroke care?

Clopidogrel is a widely prescribed antiplatelet medicine used to reduce the risk of a recurrent stroke after an ischaemic stroke or transient ischaemic attack (TIA). CYP2C19 is a liver enzyme that helps switch clopidogrel into its active, protective form. The enzyme is coded for by the CYP2C19 gene but, due to genetic variations in the gene, not everyone’s enzyme activates clopidogrel in the intended way. In the UK, around 30% of people carry a variant that reduces or even switches off CYP2C19 activity, and this rises to more than 50% in some ethnic groups. Hence, for some people, clopidogrel is far less effective than intended. CYP2C19 genotype testing helps identify who is unlikely to benefit from clopidogrel so that clinicians can choose a more suitable antiplatelet medicine from the start. It’s a clear example of how genomic information can make everyday prescribing more precise, and ultimately safer, for patients. 

Since treatment is often started immediately, the right prescription decisions must be made quickly. If a patient has a CYP2C19 variant that reduces clopidogrel activation, they may not receive adequate protection during the critical early period after a stroke, making timely testing clinically meaningful.

What the CYP2C19 pilot is telling us

This national pilot is the first large-scale assessment of how CYP2C19 testing can operate within real-world NHS stroke clinical care / management pathways. Conducted across four diverse NHS stroke services from October 2024 to April 2025, it evaluated both laboratory-based testing and point-of-care testing, generating valuable insights about feasibility, turnaround time, and prescribing impact.

Some of the early findings have been presented publicly by Genedrive, the manufacturer of one of the point of care testing platforms used in the pilot, based on data generated through the NHS evaluation. These presentations highlight several important operational observations:

• Timeliness in returning test results matters – In the point of care testing setting, all patients requiring clopidogrel had results available while still on the ward, whereas most patients undergoing laboratory testing had been discharged before results were returned.
• Point of care testing is feasible in acute settings – A low test failure rate was reported, suggesting that rapid testing can operate reliably in hyperacute stroke environments.
• Actionable variants are common – Around one third of patients tested using the point of care approach carried variants associated with reduced clopidogrel response.
• Prescribing decisions changed – Genotype results influenced prescribing choices, demonstrating clinical utility within routine pathways.

Importantly, the pilot demonstrated that both laboratory based and point of care testing models are feasible within NHS stroke pathways, each with different operational strengths and constraints. Alongside these findings, the NHS implementation guide developed by the North West Genomic Medicine Service Alliance highlights broader system considerations that will shape adoption. The guide emphasises the need for clear clinical protocols, appropriate digital infrastructure, integration with existing electronic health records, workforce training, formulary alignment, equity considerations, and effective communication with primary care to ensure that prescribing decisions are acted on consistently across care settings.

What comes next

The pilot results sit within a rapidly evolving evidence and guidance landscape. The UK Centre of Excellence for Regulatory Science and Innovation in Pharmacogenomics (CERSI PGx) has recently published updated clinical guidance on clopidogrel that includes pharmacogenomic testing. This reflects growing international consensus on the role of CYP2C19 genotype guided antiplatelet therapy and complements established recommendations from groups such as the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG). Together, these developments signal increasing maturity in the evidence base supporting CYP2C19 testing, helping move pharmacogenomics from research settings into routine clinical consideration.

These early pilot findings also arrive at a time when the NHS is re-examining how to deliver more preventative and personalised care, as set out in the 10 year plan. The plan specifically emphasises reducing avoidable illness, improving long term outcomes, and shifting more care beyond hospital settings. Pharmacogenomics sits squarely within this agenda. By helping ensure that widely prescribed medicines such as clopidogrel are effective from the outset, CYP2C19 genotype testing has the potential to reduce complications, avoid preventable readmissions, and support safer prescribing across both primary and secondary care. 

In doing so, pharmacogenomics supports a more proactive model of care, where treatment decisions are informed by individual biological differences rather than adjusted only after harm or treatment failure occurs. This aligns closely with broader NHS ambitions around population health management, prevention, and making better use of data to guide clinical decision making across care settings.

At the same time, translating this potential into routine practice is not without challenge. Integrating CYP2C19 testing into existing stroke pathways will require careful consideration of service design, workforce readiness, digital integration, and sustainable funding models, particularly given current pressures on NHS capacity and budgets.

Against this backdrop, the CYP2C19 pilot represents more than a technical evaluation of a single test. It forms part of a wider conversation about how genomic information can be embedded into everyday clinical workflows, used across organisational boundaries, and applied over a patient’s lifetime to improve outcomes. The lessons emerging from this pilot will help inform how pharmacogenomics can support more efficient care pathways, strengthen links between primary and secondary care, and shape the future integration of genomic data into routine NHS practice.