Clopidogrel, a drug that lowers the chance of having another heart attack, is frequently administered to those who have recently experienced a heart attack. Although the medication is incredibly efficient at preventing further heart attacks, it can only do so when the CYP2C19 enzyme in the body activates it. Because the body can't produce this enzyme due to certain genetic differences, clopidogrel cannot be activated by the body.
Clopidogrel not activating is actually a pretty frequent occurrence. According to estimates, one in three persons with European ancestry have one of these genetic variations; in certain ethnic groups, their prevalence is significantly higher.
For instance, one of these genetic variations is present in over 90% of Indigenous people living on Pacific island nations. They therefore most likely have a higher risk of having another heart attack if clopidogrel is administered. There haven't been many non-European population studies that connect genetic variations with actual health data, though.
Additionally, our most recent research suggests that many British south Asians may not benefit from clopidogrel. This is noteworthy since south Asian populations in the UK have high incidence of cardiovascular disease.
Genetic variants
We began our study by analysing data from 44,396 participants who’d participated in Genes & Health – a study of British-Pakistani and British-Bangladeshi people, which has linked genetic data with national records of health problems and prescriptions.
We found that nearly six in every ten people (57%) had a genetic marker that meant they would not be able to activate clopidogrel well – much higher than the 30-35% seen in people of European ancestry. Some 13% of the British-Pakistani and British-Bangladeshi people in the study had two of these genetic markers – one from each parent.
From the 44,396 participants in the study, we identified 1,006 people who had experienced a heart attack. Of these, around 69% (697 people) were prescribed clopidogrel by their GP. The majority of these participants were male.
We then sub-stratified this group by CYP2C19 genotype, and looked at participants who’d suffered recurrent heart attacks. We found that participants with recurrent heart attacks were more than three times more likely to have two clopidogrel-resistance genes as compared with none.
Genetic testing
Our study isn’t the first to suggest that clopidogrel may not be as effective for people from different ethnic groups – but it is the first to link genetic risk for decreased clopidogrel efficacy with recurrent heart attacks in a western south Asian population.
These results reiterate the importance of testing drugs on people from many different ethnic backgrounds. During its development, clopidogrel was mainly tested using people of European ancestry. This gave a skewed view of its effectiveness, especially for certain ethnic groups.
Our study also highlights the role that genetic testing can play when it comes to prescribing. Knowing what genetic variants a person has will help ensure they’re prescribed a drug that is not only effective for them, but that has minimal risk of side-effects.
Genetic testing is already available on the NHS by referral, but it is typically only done to determine a person’s risk of certain health conditions. While there are plans to offer genetic testing to stroke patients to determine if clopidogrel will work for them (the drug is also used to prevent recurrent strokes), our study suggests that expanding this genetic testing to heart attack patients would also be beneficial.
Although people in certain groups have a higher chance of having these genetic variants, it’s important to take your medication as prescribed. Clopidogrel use is still well supported by clinical evidence to prevent further heart attacks – and genetic variations are only one of many factors that affect the risks and benefits of a medication.