Guidance

1 Recommendations

1 Recommendations

1.1

Use CYP2C19 genotype testing to assess if clopidogrel is a suitable antiplatelet drug for people who have just had an ischaemic stroke or a transient ischaemic attack (TIA). CYP2C19 genotype testing is only recommended if:

  • quality-assurance processes and arrangements are in place for point-of-care tests

  • shared decision making for doing the test is established (see NICE guidance on shared decision making).

    When interpreting test results, healthcare professionals should take into account that the prevalence of different CYP2C19 genotypes may vary between ethnic groups.

Laboratory-based testing

1.2

Use laboratory-based testing for CYP2C19 genotype testing.

Point-of-care testing

1.3

Use the Genedrive CYP2C19 ID Kit point-of-care test for CYP2C19 genotype testing when laboratory-based testing is not available.

1.4

Use the Genomadix Cube point-of-care test when laboratory-based testing and the Genedrive CYP2C19 ID Kit point-of-care test are not available.

What this means in practice

This guidance does not replace existing guidance on antiplatelet therapy when genotype testing is not available, or when results from testing have not been received. Starting antiplatelet treatment should not be delayed while waiting for test results.

This guidance is not intended to affect treatment with clopidogrel that was started in the NHS before this guidance was published. People already having clopidogrel should continue until they and their NHS healthcare professional consider it appropriate to stop. The guidance recommends testing only for people just after they have had a stroke or TIA. This is because the risk of another event is higher at this time and therefore so is the potential benefit of testing. But, as the risk of recurrent stroke or TIA reduces over time, so does the benefit of testing. For this reason, retrospective testing for people already taking clopidogrel was outside of the scope of this assessment.

Implementing laboratory-based CYP2C19 genotype testing for everyone who has a stroke or TIA would result in a large population being tested, which may require testing capacity to be scaled up over time. When implementing testing, commissioners may wish to consider:

  • a phased rollout with testing initially offered to people with a higher risk of stroke recurrence who could benefit most from it, such as people who have had a non‑minor stroke

  • point-of-care testing as an alternative if laboratory-based testing is not feasible at this scale, or while capacity for laboratory-based testing is increased.

For more information about putting these recommendations into practice see section 4.

Why the committee made these recommendations

Clopidogrel is an antiplatelet drug used after ischaemic stroke or TIA (sometimes called a 'mini stroke') to reduce the risk of blood clots that can cause further strokes. Clopidogrel is metabolised into its active form by an enzyme encoded by a gene called CYP2C19. In some people CYP2C19 has variations that reduce the enzyme's function (known as 'loss-of-function' variants or alleles). This means clopidogrel does not work as well in these people. Testing for these alleles is known as CYP2C19 genotype testing. It aims to identify people with CYP2C19 loss-of-function alleles 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 alleles who have clopidogrel are more likely to have further strokes compared with people without loss-of-function CYP2C19 alleles. Clinical experts agreed that it would be beneficial to treat people with loss-of-function CYP2C19 alleles with alternative antiplatelet treatment, but the evidence was less clear on the size of this benefit. The economic evidence shows that CYP2C19 genotype testing is cost effective compared with not testing, regardless of which alternative antiplatelet therapy people have. So CYP2C19 genotype testing is recommended.

The long-term health benefits of laboratory-based and point-of-care CYP2C19 genotype testing are very similar. But, some less-common loss-of-function CYP2C19 alleles occur at a higher rate in certain ethnic groups. This means that tests that only identify the most common alleles may disproportionately fail to identify people with loss-of-function alleles in these groups. Laboratory-based testing could identify a wider range of alleles than point-of-care tests. It can also be changed more easily to test for other pharmacogenomic markers if needed. Centralised laboratory testing would also provide more consistency across the NHS. So, laboratory tests should be used if possible.

Evidence from studies provided by the company suggests that the Genedrive CYP2C19 ID Kit works well. It can detect more CYP2C19 alleles than the Genomadix Cube point-of-care test. It also:

  • does not need a freezer to store reagents

  • is cheaper per test than laboratory tests and the Genomadix Cube.

There are likely to be considerable barriers to implementing laboratory-based testing for everyone who has had an ischaemic stroke or a TIA. If laboratory-based testing is not available, or it will take a long time to develop capacity to provide it, then point-of-care tests could be used. So, the Genedrive CYP2C19 ID Kit should be used when laboratory-based testing is not available.

There is good evidence that the Genomadix Cube point-of-care test can accurately detect 2 of the most common loss-of-function CYP2C19 alleles. But it does not detect other less-common alleles, so it should only be used when laboratory-based testing and the Genedrive CYP2C19 ID Kit are not available.