Clopidogrel may be less effective in British South Asian patients, study results suggest

The study authors concluded that non-CYP2C19-dependent antiplatelet agents would likely have a "disproportionate benefit" in the British South Asian population.
Pack of anti-platelet drug clopidogrel, marketed by Sanofi as Plavix

Clopidogrel, an antiplatelet medicine, has been found to be less effective in British South Asian patients, compared to patients of European descent, research has suggested.

The genetic polymorphism study, published by the American College of Cardiology Foundation on 20 August 2023, examined the health data of 44,396 Bangladeshi and Pakistani participants from the Genes and Health cohort.

Genes and Health is a long-term study of 100,000 people of Bangladeshi and Pakistani origin, aimed to study disease and treatments in these communities.

Results from the clopidogrel study showed that 57% of cohort participants had a genetic variation of the hepatic enzyme CYP2C19, with 44% found to be intermediate metabolisers of clopidogrel and 13% found to be poor metabolisers.

The authors compared these data to figures from a previous study, which showed 2% and 8% of people of European and Central South Asian descent to be poor clopidogrel metabolisers, respectively.

CYP2C19 is involved in the metabolism of clopidogrel from a prodrug to its active metabolite. Without this metabolism, clopidogrel is unable to perform its pharmacological function. Intermediate metabolisers of the drug have one variation to the CYP2C19 enzyme, while poor metabolisers have two variations.

The study results also revealed that poor metabolisers of clopidogrel were more than three times more likely to have recurrent heart attacks (odds ratio: 3.1; P=0.019) compared to normal metabolisers of the drug.

The study authors concluded that prescribing non-CYP2C19-dependent antiplatelet agents is likely to have a “disproportionate benefit” in the British South Asian population and supported the need for pharmacogenomic testing in this group.

Lead author Emma Magavern, a clinician at Queen Mary University of London’s William Harvey Research Institute, told The Pharmaceutical Journal: “We hope that clinical practice in the UK will start to make CYP2C19 genetic testing available to clinicians to help decide what medication to prescribe after a heart attack. This is a complex decision, and many non-genetic factors are also important.

“Ideally, this testing would be pre-emptive, meaning that the genetic test results would be available at the time of prescribing.”

In May 2023, the National Institute for Health and Care Excellence (NICE) published draft guidance recommending clopidogrel genotype testing after ischaemic stroke or transient ischaemic attack (TIA).

Commenting on the study, Paul Wright, lead cardiac pharmacist at Barts Health NHS Trust, said: “In the context of a stroke or [transient ischaemic attack], clopidogrel would be selected as the antiplatelet of choice and, as such, ensuring it is effective is essential as it is the only antiplatelet being given.

“The use of clopidogrel in patients presenting with acute myocardial infarction is now mostly superseded by the more potent antiplatelets (prasugrel or ticagrelor) that do not have dependency on CYP2C19 for effectiveness and, as such, testing for polymorphism in this context may not be needed,” he added.

As a pilot initiative, NHS Tayside has already started using gene testing for clopidogrel suitability — the first healthcare system in the UK to do so.

Vicky Ruszala, specialist pharmacist in cardiology and heart failure at North Bristol NHS Trust, said that pharmacogenomic testing of clopidogrel is required in everyone, not just in the South Asian population. “It’s just not affordable for us to do that in the UK,” she said.

Ruszala also raised concerns on the practicality of pharmacogenomic testing.

“So, somebody who comes in with a heart attack or stroke will have treatment initiated within the first 24 hours,” she said.

“The genotype testing often takes two days to come back and the patient’s already been discharged.

“Is it up to the GP to call them back in and make some kind of adjustments? Or does the patient have to come back into the cardiology outpatient clinics to have a discharge?”

Last updated
The Pharmaceutical Journal, PJ, August 2023, Vol 311, No 7976;311(7976)::DOI:10.1211/PJ.2023.1.195433

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