Clopidogrel Testing: New UK Genetic Guideline

The UK Center of Excellence in Regulatory Science and Innovation in Pharmacogenomics (UK CERSI-PGx), led by the University of Liverpool, has published its first clinical guideline focused on the use of the antiplatelet medication clopidogrel, widely prescribed in the U.K. to prevent blood clots. Pharmacogenomics looks at how differences in our genes can change the way medicines affect each person.

The guidelines and a related editorial are published on 4 December 2025 in the British Journal of Clinical Pharmacology.

The guideline addresses CYP2C19 genotyping in patients prescribed clopidogrel for conditions such as coronary artery disease, cerebrovascular disease, and peripheral arterial disease. This is because clopidogrel does not work uniformly in all patients.

CYP2C19 is an enzyme in the liver that influences how clopidogrel is converted in the body into its active form. Different people have different levels of this enzyme because of variation in their CYP2C19 gene. Those with low enzyme levels will activate clopidogrel less efficiently than those with “normal” levels, making clopidogrel less effective—this variability can be detected by a simple genetic test. A significant proportion of the population have lower enzyme levels: in white individuals it is 20%–30%, but it can be as high as 50%–60% in those of Asian descent.

Rather than duplicating existing international pharmacogenomic guidelines from CPIC and DPWG, the UK CERSI-PGx guideline provides a greater clinical focus, offering practical recommendations on:

• Eligibility for testing
• Integration into current clinical pathways
• Variants to test and turnaround times
• Actions based on genotype
• Health economic considerations
• Evidence gaps and future research priorities

The development of these guidelines is a first for the U.K. and has been undertaken by a committee with a representative group of specialists. These guidelines will be important for regulators, for industry and for the NHS. The NHS 10-year plan states that “pharmacogenomics will be integrated into routine clinical practice”—the current guideline, and the others which are currently in development by CERSI-PGx, will help with that ambition.

Center Lead, the University of Liverpool’s Professor Sir Munir Pirmohamed, said, “With the new CERSI-PGx guideline for clopidogrel, we aim to ensure patients are prescribed the right treatment at the right dose, based on their genetics. By integrating CYP2C19 testing into routine pathways, we can improve efficacy, reduce adverse drug reactions, ease pressure on the NHS, and support cost-effective, precision prescribing.”

Professor Dame Sue Hill, Chief Scientific Officer for England said, “These guidelines are an important step in using genomics to inform treatment pathways and to prevent avoidable side effects. I am delighted that an inclusive and multidisciplinary approach was taken to support the development of these guidelines and that this approach will be used for other clinical use cases. The availability of U.K. clinical guidelines for pharmacogenomics will enable the systematic introduction into mainstream care.”

MHRA’s Chief Safety Officer, Dr. Alison Cave, said, “This first clinical guideline from UK-CERSI-PGx for clopidogrel provides practical recommendations to accelerate the integration of pharmacogenomics into routine care. By analyzing a patient’s genetic information, pharmacogenomics ensures they receive the most appropriate medication and dosage for their specific genetic profile, minimizing the risk of adverse drug reactions.

“Such approaches form part of MHRA’s long-term vision for more personalized medicine prescribing and will be a gamechanger for patient safety and well-being.”