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A genetic study has revealed how the use of clopidogrel in British patients of south Asian ancestry appears to be less effective at preventing recurrent myocardial infarction than in those of European descent.
The study, which was published in the journal JACC: Advances, sought to assess the prevalence of common CYP2C19 genotype polymorphisms in a British south Asian population and correlate these with recurrent myocardial infarction risk in participants prescribed clopidogrel.
Researchers used data from the East London Genes & Health (ELGH) database – a community-based, long-term study of health and disease in British Bangladeshi and British Pakistani people in east London. ELGH incorporates cutting-edge genomics with electronic health record data linkage and targeted recall-by-genotype studies.
Clopidogrel CYP2C19 polymorphism
Using data from 44,396 individuals, researchers found a high prevalence (57%) of intermediate or poor CYP2C19 metabolisers, with at least one loss-of-function CYP2C19 allele.
In addition, the prevalence of poor metabolisers, characterised by two CYP2C19 loss-of-function alleles was 13%, which was higher than that in previously studied European (2.4%) and central/south Asian populations (8.2%).
In the cohort, 69% were diagnosed with an acute myocardial infarction and prescribed clopidogrel. Poor metabolisers were found to be significantly more likely to have a recurrent myocardial infarction (Odds ratio, OR = 3.1, 95% CI 1.2 – 8.1, p = 0.019).
Dr Emma Magavern, lead author from Queen Mary University of London, said: ‘This study highlights the importance of using genetics to determine who can benefit from clopidogrel after a heart attack, and how not doing so is likely to disproportionately disadvantage specific groups, such as south Asians.
‘British peoples of south Asian ancestry suffer from high rates of cardiovascular disease and therefore have both a high risk of needing an anti-platelet medication and a high risk of treatment failure with clopidogrel.’
The P2Y12-inhibiting agent clopidogrel, which can be used post-myocardial infarction to reduce the risk of a second infarction, as well as to lower the risk of bleeding following a percutaneous coronary invention, is metabolised by the hepatic enzyme CYP2C19. This transformation converts the inactive pro-drug into an active metabolite.
