Clopidogrel genotype testing after ischaemic stroke or transient ischaemic attack

1 Recommendations

1.1 Offer laboratory-based clopidogrel genotype testing, or the Genomadix Cube point-of-care test if laboratory testing is not possible, to people who have had an ischaemic stroke or transient ischaemic attack if treatment with clopidogrel is being considered.

1.2 Healthcare professionals should take into account that the prevalence of different CYP2C19 genotypes may vary between ethnic groups.

1.3 There is not enough evidence to recommend the Genedrive CYP2C19 ID Kit. It should only be used in the context of research.

1.4 Further research is recommended on the Genedrive CYP2C19 ID Kit to determine its accuracy and failure rate (see the section on further research).

Why the committee made these recommendations

Clopidogrel is an antiplatelet drug used after ischaemic stroke or transient ischaemic attack (sometimes called a 'mini stroke') to reduce the risk of blood clots that can cause further strokes or heart attacks. But clopidogrel does not work as well in some people because they have variations in a gene called CYP2C19 (known as 'loss-of-function variants'). Clopidogrel genotype testing can identify these people so they can be offered alternative antiplatelet drugs to lower their risk of blood clots. Testing can be done in a laboratory or at the point of care (for example, on a stroke ward).

There is good clinical evidence that people with loss-of-function CYP2C19 variants who have clopidogrel are more likely to have further blood clots compared with people without loss-of-function CYP2C19 variants. Clinical experts agreed that it would be beneficial to treat people with loss-of-function CYP2C19 variants with alternative antiplatelet treatment, but the evidence was less clear on the size of this benefit. The economic evidence shows that clopidogrel genotype testing is cost effective compared with not testing, regardless of which alternative antiplatelet therapy people have. So clopidogrel genotype testing is recommended.

There is good evidence that the Genomadix Cube point-of-care test can accurately detect 2 of the most common loss-of-function CYP2C19 variants. But it does not detect other less common variants. It is also more expensive per test than laboratory testing.

The long-term health benefits of laboratory-based and point-of-care clopidogrel genotype testing are very similar. But, some less common loss-of-function CYP2C19 variants occur at a higher rate in certain ethnic groups. This means that tests that only identify the most common variants may disproportionately misdiagnose people in these groups. So, because they can detect a wider range of variants and are likely to cost less, laboratory tests should be used if possible.

There is no data on the Genedrive CYP2C19 ID Kit. More evidence is needed on how well it works. It does not yet have regulatory approval and is only recommended for further research in this draft guidance because the company indicated that approval is expected in the next 12 months. This test will only be included in the final guidance if it has appropriate regulatory approval by the date of final guidance publication.