<i>CYP2C19</i> genotype testing for clopidogrel: A guideline developed by the UK Centre of Excellence in Regulatory Science and Innovation in Pharmacogenomics (CERSI‐PGx)
Clopidogrel, an antiplatelet agent, is currently licensed in the United Kingdom for the prevention and treatment of atherothrombotic events in cerebrovascular disease, coronary artery disease and peripheral arterial disease. Clopidogrel requires metabolic activation by the cytochrome P450 enzyme CYP2C19 to be effective. CYP2C19 is encoded by a polymorphic gene; variants in the CYP2C19 gene, which vary in frequency in different ethnic groups can abolish, reduce or increase enzyme activity, thereby affecting the conversion of clopidogrel to its active metabolite. Individuals who have either one or two loss-of-function alleles are referred to as intermediate and poor metabolisers, respectively, and in these patients, the clinical effectiveness of clopidogrel is reduced or absent. Any patient about to be prescribed clopidogrel, regardless of the underlying indication, should have pharmacogenetic testing to identify clinically relevant CYP2C19 variants, where testing is available, to optimize their antiplatelet therapy. Clopidogrel use should be avoided in patients with an intermediate or poor CYP2C19 metaboliser phenotype in all approved indications and alternative treatment regimens used as detailed in this guideline. Our guideline is compatible with other international pharmacogenetic prescribing guidelines, but we also provide recommendations in other areas. Summary guidance on a page is provided for each of the indications in Boxes 1-3. This guideline is grounded in the latest evidence in this field but cannot account for all individual factors relevant to patient care. Therefore, prescribers must conduct a thorough assessment of each patient's risk-benefit profile, ensuring that therapy is optimized to maximize benefits while minimizing potential harms.
Authors
- Cinzia Dello Russo (ORCID: https://orcid.org/0000-0002-2538-3832)
- Thomas Alexander Hughes (ORCID: https://orcid.org/0000-0003-1169-3386)
- Alex S. F. Doney (ORCID: https://orcid.org/0000-0002-6210-5620)
- Kerry A. Burke (ORCID: https://orcid.org/0009-0002-8678-8865)
- Sophie Harding (ORCID: https://orcid.org/0000-0002-2221-6684)
- Simon Ray (ORCID: https://orcid.org/0000-0001-7775-1900)
- David R. Hargroves (ORCID: https://orcid.org/0000-0003-0127-3011)
- Luigi A. Venetucci (ORCID: https://orcid.org/0000-0002-8236-3993)
- Imran Rafi (ORCID: https://orcid.org/0000-0001-9673-9675)
- Rebecca Kuruvilla
- Dyfrig Hughes (ORCID: https://orcid.org/0000-0001-8247-7459)
- Nicholas S. Greaves (ORCID: https://orcid.org/0000-0002-5646-9364)
- Aaron Peace (ORCID: https://orcid.org/0000-0001-9556-7509)
- Victoria Stinton
- Salim Elyas (ORCID: https://orcid.org/0000-0002-0303-720X)
- Judith Hayward (ORCID: https://orcid.org/0000-0001-7137-1261)
- Stefanie Lip (ORCID: https://orcid.org/0000-0001-8515-9018)
- H. J. O’Neill (ORCID: https://orcid.org/0000-0003-3982-6515)
- Paul Kan Hwei Mok
- Iain Frater (ORCID: https://orcid.org/0009-0003-3941-8375)
- Sree Kondapally
- Vicky Chaplin
Institutions
- Università Cattolica del Sacro Cuore (IT)
- Cardiff and Vale University Health Board (GB)
- University of Ulster (GB)
- University of Liverpool (GB)
- Bangor University (GB)
- St George's, University of London (GB)
- University of Dundee (GB)
- University of Exeter (GB)
- Royal Devon & Exeter NHS Foundation Trust (GB)
- University Hospital of Wales (GB)
- St George’s University Hospitals NHS Foundation Trust (GB)
- Manchester Royal Infirmary (GB)
- Agostino Gemelli University Polyclinic (IT)
- East Kent Hospitals University NHS Foundation Trust (GB)
- University of Manchester (GB)
- St Mary's Hospital (GB)
- Manchester University NHS Foundation Trust (GB)
- Western Health and Social Care Trust (GB)
- St Mary's Hospital (GB)
- Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust (GB)
- Health Education North West (GB)
- NIHR Exeter Clinical Research Facility (GB)
- Genomics England (GB)
- Velindre Cancer Centre (GB)
- Genomics (United Kingdom) (GB)
- Queen Elizabeth University Hospital (GB)
- St. Mary's Hospital (GB)
- NHS England
- University of Glasgow (GB)
Publication Details
- Journal
- British Journal of Clinical Pharmacology
- Published
- 2025-12-03
- DOI
- https://doi.org/10.1002/bcp.70370
- Citations
- 2
- Primary Topic
- Antiplatelet Therapy and Cardiovascular Diseases
- Type
- article
- Field-Weighted Citation Impact
- 2.78
Funders
- UK Research and Innovation
- Center of Excellence in Regulatory Science and Innovation