Your article (Doctors find drug that is better than aspirin at preventing heart attacks, 31 August) is of great interest. It cites a study that proposes replacing aspirin, the cornerstone of antiplatelet therapy for individuals at high risk of heart attacks and strokes, with clopidogrel. We must point out, however, that clopidogrel does not work uniformly across individuals. Although mentioned in the Lancet publication, it was only lightly considered in the Guardian article.
Clopidogrel is a prodrug. To work, it needs to be metabolised by a liver enzyme that varies in the population because of variations in the CYP2C19 gene. Most individuals have “normal” or “supra-normal” levels of the enzyme and clopidogrel works as expected. However, “intermediate metabolisers” activate clopidogrel less efficiently and “poor metabolisers” struggle to activate clopidogrel at all. For these people, clopidogrel may not provide enough protection against heart attacks or strokes.
This issue is not academic: 20%-30% of white individuals in the UK are intermediate or poor metabolisers and in Asian populations this can be as high as 50%-60%. Ignoring individual genetic differences may also have legal implications. In 2024, Hawaii won a landmark lawsuit against clopidogrel manufacturers for failing to disclose the efficacy and safety profile of the drug considering that a large percentage of the Hawaiian population are intermediate or poor metabolisers.
In summary, clopidogrel’s effectiveness is not universal and a “one-drug-fits-all” approach may expose patients to preventable harm. Individuals can be tested for genetic variation in the CYP2C19 gene, enabling a personalised approach. Patients with normal or supra-normal levels of the enzyme can be treated with clopidogrel as standard for the long term, while those with lower enzyme levels can continue with aspirin, the current standard. Such a personalised approach may even provide better outcomes than those reported in the Lancet paper.
Dr Ronnie Ramlogan, Dr Dimitri Gagliardi, Dr Luigi Venetucci, Dr Abisope Akintola University of Manchester, Dr Cinzia Dello Russo, Prof Sir Munir Pirmohamed University of Liverpool
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