By: Mark Delabajan
The patient was a South Asian man in his mid-sixties. He was a devoted husband, father and grandfather who continued to work hard for his family despite a growing list of health challenges. To those around him he embodied resilience, though beneath the surface he was living with an increasingly complex cardiovascular history that would challenge his clinicians.
His first warning sign came in 2010 when he experienced a transient ischaemic attack (TIA). He recovered well and was prescribed clopidogrel for secondary prevention. Five years later, he suffered a stroke, followed by a heart attack in 2018. In 2022, he experienced a further three TIAs, and by 2024 had suffered another stroke despite remaining compliant with his prescribed antiplatelet therapy.
A search for answers
In April 2024, the patient was brought back to hospital with acute symptoms suggestive of another stroke. Fortunately, he arrived in time to receive thrombolysis, a clot-dissolving treatment that can restore blood flow to the brain if given quickly, and was treated promptly. As the team reviewed his investigations, a striking picture emerged. Brain imaging showed evidence of multiple strokes, some recent and others older, affecting several different blood vessel territories and involving almost every lope of the brain. Yet no clear cause emerged. An ultrasound of the neck arteries showed no significant narrowing, heart investigations and rhythm monitoring found no source of clots in the heart, and further tests for blood vessel inflammation and clotting disorders offered little insight into why he continued to suffer recurrent vascular events.
For the stroke team, the question became hard to ignore: how could a patient who had taken clopidogrel for over a decade continue to experience recurrent strokes, TIAs and a heart attack?
Why clopidogrel doesn’t work for everyone
No single test could provide a definitive answer. But this patient’s story pointed to something gaining increasing attention – variation in how individuals metabolise and respond to medications.
Clopidogrel is one of the most widely prescribed antiplatelet agents in the world, helping patients by preventing clot formation and reducing the risk of recurrent cardiovascular and cerebrovascular events. However, it is a prodrug, meaning it requires activation by the CYP2C19 enzyme before it can exert its therapeutic effect.
For some individuals, inherited genetic variations within the CYP2C19 gene reduce this activation process, so the drug may not provide the level of platelet inhibition expected, potentially leaving patients at higher risk of recurrent events despite appearing to receive appropriate treatment.
Crucially, these variants are not evenly distributed across populations: studies show higher frequencies of these variants among certain ethnic groups, including many South Asian and East Asian populations. This raises important questions about whether some communities are disproportionately affected by reduced responsiveness to clopidogrel and whether they may benefit from earlier access to pharmacogenetic testing.
From standardised treatment to personalised medicine
This case does not prove that CYP2C19 loss-of-function was responsible for his recurrent strokes and cardiovascular events. Multiple factors contribute to vascular risk, and it would be impossible to retrospectively determine the precise role genetics played in his individual health journey.
But the example illustrates a broader challenge facing modern healthcare, which have long relied on standardised treatment pathways built around what works for most people. While this approach has been enormously successful, it does not always account for biological differences between individuals and populations, with advances in genomics increasingly showing the same treatment can produce different outcomes in different patients.
This is where personalised medicine has the potential to transform care. Pharmacogenetic testing, such as CYP2C19 analysis, gives clinicians an additional layer of information to support treatment decisions. By identifying patients who may have reduced responsiveness to clopidogrel, clinicians can consider alternative treatments, moving beyond a “one-size-fits-all” approach towards treatment plans that reflect each patient’s biology.
For communities that have historically experienced poorer health outcomes, this is a huge opportunity. Personalised medicine is not simply about innovation but also about equity, ensuring advances in science benefit all populations rather than widening existing disparities.
Behind every discussion about genomics, pharmacogenetics and health inequalities is a real person and their family, underscoring the importance of tailored, evidence-based care so all patients, regardless of ethnicity or background, receive the right treatment and the best possible care.
A clinician’s perspective
With healthcare entering the genomics era, as clinicians we increasingly recognise that genetic variation can influence treatment effectiveness. CYP2C19 testing offers an opportunity to move beyond empirical prescribing towards a more personalised approach, helping us select the most appropriate therapy from the outset.
As clinicians serving different populations and ethnicities, this is also a health inequalities issue we can act on now. Making pharmacogenetic testing routinely available, rather than reserved for complex or unexplained cases like this patient’s, would let us catch reduced clopidogrel response before a patient has suffered repeated strokes, not after.
But the promise here goes further than clinical outcomes alone. Wider use of pharmacogenetic testing could spare patients from avoidable strokes and ineffective treatment, give them real confidence that their care is built around their own biology rather than an average, and make far better use of stretched healthcare resources in the process.
As stroke services continue to evolve, I believe the case for embedding CYP2C19 testing into everyday clinical practice is clear. The question is simply how quickly we do.
