What is Clopidogrel?
Clopidogrel is a type of blood thinner anti-platelet drug used to prevent blood clots in people who have had heart attacks, strokes, or stents placed.
How Does Clopidogrel Work?
Clopidogrel is a prodrug, which means the body metabolises it into an active drug.
It gets turned into its active form by an enzyme from a gene called CYP2C19. Some people have variations in this gene (known as ‘loss-of-function’ variants or alleles). that reduce the enzyme’s activity, which means clopidogrel might not work as well for them. Testing for these variations, known as CYP2C19 genotype testing, helps identify those who might need different medications to reduce their risk of blood clots. This test can be done in a lab or sometimes right at the point of care, like in a stroke ward.
What is NICE?
In the UK, NICE (the National Institute for Health and Care Excellence) decides which treatments are cost-effective and should be funded by the government.
NICE suggests testing for CYP2C19 gene variations in new cases of transient ischemic attack (TIA) or stroke. Retrospective testing for people already on Clopidogrel wasn’t included in their assessment.
There is solid evidence that people with loss-of-function CYP2C19 alleles who are on clopidogrel are more likely to have further strokes compared to those without these gene variations. Evidence for heart attack or stent patients is less clear. Clinical experts agree that switching to alternative antiplatelet treatments for those with loss-of-function alleles could be beneficial, but the extent of this benefit isn’t fully established.
If someone has a recurrent stroke or TIA while on clopidogrel, it might be worth checking for these gene variations, especially if other reasons, like non-adherence to the prescribed treatment, have been ruled out.
What are the Alternatives to Clopidogrel?
After a stroke, you could take aspirin combined with dipyridamole, which is considered safe. Ticagrelor and prasugrel are also options after stroke and TIA, but they come with a higher risk of bleeding.
Is it Cost-Effective to Test for Resistance?
Economic evidence suggests that CYP2C19 genotype testing is cost-effective compared to not testing, regardless of the alternative antiplatelet therapy chosen. Therefore, testing is recommended for those about to start clopidogrel.
Should I stop Clopidogrel until I Get Tested?
Please don’t stop taking Clopidogrel if you’re currently taking it. It’s likely working well for you. If you have concerns, speak to your cardiologist or stroke specialist. If you’ve been on Clopidogrel for a long time without issues, it’s less likely that you have loss-of-function alleles. The risk of recurrent stroke, or TIA, is highest within the first 12 weeks of treatment.
Which Test Should I Take?
Keep in mind that tests vary in which gene variations they can detect. They look for specific gene variations, and NOT measure if clopidogrel is working as an anti-platelet. For example, some tests check for variations like *2, *3, *4, *8, *17, and *35. If you have other variations, this test might not detect them.
Note that some racial groups, e.g. South Asians, might be at higher risk of clopidogrel resistance.
