Reducing stroke risk with a genetic test

NHS Tayside introduces UK’s first routine genetic test for stroke patients, estimated to bring improved outcomes to thousands of patients each year

An NHS health board in Scotland is the first in the country to introduce genetic testing as part of its routine care for stroke patients at NHS Tayside’s Ninewells Hospital.

The test, developed by East of Scotland Regional Genetic Laboratory, will be used to assess if clopidogrel should be prescribed to newly admitted stroke patients. NHS Tayside estimates that the test will lead to improved outcomes for about 400 patients with heart disease and 600 stroke patients each year.

Clopidogrel and strokes

A stroke happens when the blood supply to part of the brain is cut off, which is often caused by a blood clot causing a blockage in a blood vessel. Anti-clotting drugs, such as clopidogrel, reduce the risk of further strokes in people who have previously been affected. They are an important part of preventative stroke treatment.

Clopidogrel helps to prevent blood clots from forming by making it harder for platelets – blood cells that help in clotting – bind together. It is a first-line treatment for reducing the risk of blood clots in people who have had a stroke or another cardiovascular event, such as a heart attack.

Clopidogrel, however, is less effective in about a quarter of stroke patients; they possess a genetic variant that mean they process the drug differently. They are therefore at a greater risk of further strokes unless they can be identified and an alternative anti-clotting drug is prescribed.

The role of CYP2C19

Variants in the CYP2C19 gene can affect how clopidogrel works in the body. CYP2C19 codes for the CYP2C19 enzyme. It is expressed in the liver, which is involved in processing many types of drugs.

Clopidogrel is a pro-drug, meaning that it is not administered in its active form. Instead, it must be metabolised within the liver by the CYP2C19 enzyme, to activate it.

People with a CYP2C19 variant that reduces enzymatic activity do not convert enough clopidogrel to the active form to reduce clotting. They are therefore at an increased risk of further strokes after an initial event. It is, however, possible to use a genetic test to predict a person’s level of CYP2C19 enzyme activity and consequently their response to clopidogrel.

Genetic testing for Tayside stroke patients

Evolving from a smaller trial within SHARE – the Scottish Health Research Register and Biobank – CYP2C19 gene testing is now being included in the standard care pathways for stroke patients at NHS Tayside’s Ninewells Hospital. The health board expects that the test “will support improved outcomes for around 600 stroke patients and 400 patients with heart disease, each year”.

New patients being admitted to Ninewells Hospital for stroke will be offered a genetic test if their clinician is considering prescribing clopidogrel. The tests will be carried out by East of Scotland Regional Genetic Laboratory.

“NHS Tayside’s genetic testing of stroke patients through a simple blood test is the first step towards translating clinical research into much wider use of genetic information in everyday healthcare, which will help make routinely prescribed medicines more safe and effective for individual patients,” said NHS Tayside’s honorary consultant stroke physician Dr Alex Doney.

Further applications

Having a patient’s CYP2C19 gene variant on their medical records could have other advantages. For instance, up to 10% of commonly prescribed drugs are metabolised by CYP2C19 in the body, such as proton-pump inhibitors (used to reduce stomach acid production), benzodiazepines (for example, diazepam) and some antidepressants.

To know a patient’s CYP2C19 gene variant could help clinicians predict their reaction to these drugs and reduce unwanted side-effects, leading to more positive patient outcomes.

Please note: This article is for informational or educational purposes, and does not substitute professional medical advice.