NHS England: Clopidogrel & PGx
NHS England has published a useful resource on the commonly prescribed antiplatelet medication, Clopidogrel, and how genetic variations can impact its efficacy. Below, we’ve highlighted some of the key points raised in the article:
Clinical Context:
Clopidogrel is a widely used antiplatelet medication prescribed for coronary artery disease, peripheral vascular disease, and after ischemic strokes or transient ischemic attacks to prevent further vascular events.
Clopidogrel and Pharmacogenomics:
Clopidogrel is a prodrug that requires conversion to its active form through oxidative metabolism, primarily involving the CYP2C19 enzyme.
Genetic variations in the CYP2C19 gene significantly impact the efficacy of clopidogrel.
Patients with two loss-of-function CYP2C19 alleles are classified as poor metabolisers, leading to ineffective clopidogrel activation and increased risk of cardiovascular events.
Those with one loss-of-function allele are intermediate metabolisers, also experiencing reduced clopidogrel effectiveness.
Genomic Testing for CYP2C19 Variation:
Current NHS guidelines do not mandate CYP2C19 testing before starting clopidogrel therapy for cardiovascular disease.
However, CPIC guidelines recommend considering alternative antiplatelet agents like prasugrel or ticagrelor for intermediate and poor metabolisers.
Genotype-guided therapy can help identify patients who would benefit more from these alternative medications.
Practical Implications:
Clinicians are advised to avoid clopidogrel in patients with acute coronary syndrome or percutaneous coronary intervention who have a CYP2C19 intermediate or poor metaboliser phenotype, opting instead for prasugrel or ticagrelor.
The article includes a summary of CPIC 2022 recommendations for prescribing clopidogrel based on CYP2C19 phenotype.
For the full article and detailed guidelines, click on the link below: