CYP2C19 genotype testing to guide clopidogrel use after ischaemic stroke or transient ischaemic attack

Overview

People who have had an ischaemic stroke or TIA (Transient Ischaemic Attack, sometimes called a 'mini stroke') are at increased risk of further occlusive vascular events including heart attacks and peripheral vascular disease, particularly those caused by platelet-based blood clots. Clopidogrel is an antiplatelet medicine that is prescribed to reduce this risk and is widely recommended in clinical guidelines for managing stroke.

Clopidogrel is a "pro-drug" which means it must be metabolised into its active form to be effective. This is largely done by an enzyme encoded by a gene called CYP2C19. Up to 30% of people in the UK carry variants of CYP2C19 that reduce the enzyme's function, known as 'loss-of-function' (LOF) variants. This means in these people clopidogrel does not work as well and it has been clinically established that they have a greater risk of recurrent events when prescribed clopidogrel than patients not carrying such variants. Furthermore, alternative antiplatelet medicines are available that are not affected in this way. A simple genetic test can identify patients carrying LOF variants who can be then offered these alternative antiplatelet medicines that will work for them. LOF variants are more common in certain ethnic groups, such as people with an Asian family background.

In common with current standard care for patients with stroke in the UK, prior to implementation of the CYP2C19 genotype testing in NHS Tayside, clopidogrel therapy was prescribed without knowledge of which patients carried LOF variants. This exposes a significant number of people to potential harm because the clopidogrel is not working as desired.

Testing in this way for LOF variants in people who have had stroke is an example of Pharmacogenomics which makes use of an individual patient's genetic information to individually optimise the safety and effectiveness of the medications they are prescribed. In this way Pharmacogenomics can improve health outcomes and to help address health inequalities.