Published: 24 August 2023
A new study has found that a medication commonly prescribed to prevent heart attacks is much less likely to benefit people of Bangladeshi and Pakistani ancestry, compared to people of European descent.
The research was completed at Queen Mary University of London. It was funded by the NIHR Barts Biomedical Research Centre and Barts Charity. The study highlights the importance of understanding how treatments affect different ancestral groups. This is key to ensuring that everyone has equal access to effective treatments.
Searching for genetic variants
Clopidogrel is commonly prescribed to patients after a heart attack to prevent further attacks. It works by stopping blood cells known as platelets from sticking together. This helps to prevent dangerous blood clots from forming. Clopidogrel needs to be activated in the body to be effective. Studies of European populations show that 30% of people have changes in their genes, known as genetic variants, that reduce or prevent activation through the production of an enzyme called CYP2C19.
People of South Asian ancestry have high rates of cardiovascular disease. However, researchers have not looked for these variants in UK South Asian populations.
The researchers examined the health data of 44,396 British people of Bangladeshi and Pakistani ancestry. All participants were from the Genes & Health cohort. They found that 57% of participants have the common genetic change that means they cannot activate clopidogrel. More than two in three British South Asians in the Genes & Health cohort who have had a heart attack received clopidogrel.
Using the participants’ long-term health data, the research team was able to show that people with two loss-of-function CYP2C19 variants were more than three times more likely to have recurrent heart attacks. This may be because treatment with clopidogrel doesn’t work for them.
The cost of under-representation in trials
Dr Emma Magavern, lead author and clinical doctor and researcher at Queen Mary University of London, said: “Clopidogrel has been shown to prevent heart attacks mainly in people of European ancestry. For the first time we show that genetic variants that render clopidogrel ineffective are present at much higher rates (57%) in British people of Bangladeshi and Pakistani ancestry and are linked with higher risk of having another heart attack in people prescribed clopidogrel.
“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 antiplatelet medication and a high risk of treatment failure with clopidogrel. This study also illustrates how systemic under-representation of South Asians in therapeutics trials has obscured the intersection of risks impacting this community.”
The study has been published in JACC: Advances
Further reading: Diversity in research matters