CYP2C19 genotype testing for clopidogrel: A guideline developed by the UK Centre of Excellence in Regulatory Science and Innovation in Pharmacogenomics (CERSI‐PGx)
Year: 2025
Type: article
Abstract: 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.
DOI: 10.1002/bcp.70370
Authors: Cinzia Dello Russo, Iain Frater, Rebecca Kuruvilla, Stefanie Lip, Hannah O'Neill, Kerry Burke, Vicky Chaplin, Alexander S. F. Doney, Salim Elyas, Nicholas Greaves, Sophie Harding, David Hargroves, Judith Hayward, Dyfrig A. Hughes, Tom A. T. Hughes, Sree Kondapally, Patrick Mok, Aaron Peace, Imran Rafi, Simon Ray, Vicky Stinton, Luigi Venetucci, Munir Pirmohamed
Institutions: Università Cattolica del Sacro Cuore, University of Liverpool, Agostino Gemelli University Polyclinic, Istituti di Ricovero e Cura a Carattere Scientifico, University of Glasgow, Queen Elizabeth University Hospital, University of Dundee, Manchester Royal Infirmary, University of Manchester, St Mary's Hospital, Manchester University NHS Foundation Trust, NHS England, University of Exeter, Royal Devon & Exeter NHS Foundation Trust, Royal Devon University Healthcare NHS Foundation Trust, Velindre Cancer Centre, East Kent Hospitals University NHS Foundation Trust, Bangor University, University Hospital of Wales, St George's, University of London, St George’s University Hospitals NHS Foundation Trust, Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust, University of Ulster, Western Health and Social Care Trust, Ulster University, Derry-Londonderry Campus
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,780
OpenAlex ID: W4416971524