How Can Pharmacogenomics (PGx) Help With Stroke Prevention?

What is a stroke?

The brain relies on a consistent supply of oxygen and nutrients delivered through the bloodstream to function. A stroke occurs when blood flow to the brain is disrupted or there is sudden bleeding in the brain, causing brain cells to start dying or be severely damaged within minutes. There are two major kinds of stroke, both of which cause parts of the brain to stop functioning properly:

1. 1. Ischaemic strokes account for the majority of stroke cases (85%) and are caused by blood clots blocking arteries to the brain.
   2. Haemorrhagic strokes result from bleeding in the brain due to ruptured blood vessels, causing pressure on brain cells which in turn damages them.

A transient ischaemic attack (TIA), often referred to as a “mini-stroke,” is a related condition that entails a temporary disruption of blood flow to the brain, serving as a warning sign for potential strokes. TIAs usually persist no longer than 5 minutes.

Common risk factors for stroke include hypertension, diabetes, high cholesterol, smoking, obesity, sedentary lifestyle, and excessive alcohol consumption. Age, family history, race, and gender also influence stroke risk.

Stroke is a medical emergency and is a leading cause of disability and death worldwide. It is recommended for patients who have suffered a TIA in the past or are particularly at risk of stroke to take preventative measures including certain prescribed medications.

What medicines are usually taken to help prevent a stroke?

In addition to lifestyle modifications such as maintaining a healthy diet low in saturated fats and sodium, engaging in regular physical activity, quitting smoking, and limiting alcohol intake, there are medications that can be prescribed for individuals at high risk of stroke.

These may include antiplatelet or anticoagulant medications to prevent blood clots such as Clopidogrel, Aspirin, Warfarin or Acenocoumarol; blood pressure-lowering medications including ARBs and ACE inhibitors and beta-blockers, such as Metoprolol or Atenolol; and cholesterol-lowering drugs such as Atorvastatin or Simvastatin.

What are the common side effects of taking medicines for stroke prevention?

Below is a list of some of the common side effects of different stroke prevention medications. Please note, this is not a full list of potential side effects. Please speak to a health professional if you have any concerns about potential side effects.

Antiplatelets

• Headaches
• Heart palpitations
• Diarrhoea
• Stomach pains
• Indigestion or heartburn
• Bleeding more easily than normal e.g. nosebleeds, bruising more easily, taking longer to stop bleeding than usual
  

   

  Anticoagulants

  • Excessive bleeding

     

  • Constipation
  • Diarrhoea
  • Dizziness
  • Indigestion
  • Rashes
  • Itchy skin
  • Jaundice
  • Hair loss
  • Nausea and vomiting
    

     

    Statins

  • Nausea
  • Dizziness
  • Feeling weak
  • Muscular aches and pains
  • Constipation
  • Diarrhoea
  • Indigestion
  • Farting
  • Sleep problems
  • Headache
  • Blood pressure medication
  • Erection issues
  • Headaches
  • Skin rashes
  • Tiredness or fatigue
  • Insomnia and sleep problems
  • Dizziness
  • Palpitations
  • Depression
  • Nervousness

  The problem with Clopidogrel

  In the UK, one of the most commonly prescribed anti-clot medications for stroke prevention is Clopidogrel, which is activated in the liver by special enzymes called CYP2C19.

  Genetic differences cause CYP2C19 enzymes to behave differently, which means they don’t activate Clopidogrel properly. This can make the medication less effective in preventing blood clots for these individuals, known as ‘poor metabolisers.’

  Research shows that clopidogrel does not work in 32% of the British population. In East Asian individuals, this figure is even higher.

  If someone is found to be a poor metaboliser, doctors may consider using a different medication to prevent strokes.

  What is Pharmacogenomics (PGx)?

  As explained above, our DNA affects how our bodies respond to medicine. Not all medications are universally effective: some only work on a minority of individuals, some require adjusted dosages, and others carry the risk of unwanted side effects.

  Pharmacogenomic (PGx) testing allows healthcare professionals to write personalised prescriptions and determine optimal dosages based on an individual’s DNA, maximising the likelihood of effectiveness, and minimising the risk of adverse reactions.

  How can Pharmacogenomics (PGx) help?

  Recent advancements in pharmacogenomics (PGx) have revealed that our genetic makeup can significantly influence how our bodies respond to medications and our susceptibility to potential side effects. As each individual carries unique genetic variations, identifying specific gene variants is crucial for healthcare professionals when determining the most suitable medication for their patients.

  Currently, prescribing medications often involves a trial-and-error approach, with doctors making educated guesses based on limited information. However, PGx testing eliminates this guesswork by providing comprehensive insights into an individual’s genetic profile.

  When it comes to Clopidogrel, for instance, PGx testing can identify people who are poor metabolisers of CYP2C19. PGx test results will give healthcare professionals valuable genetic information as to whether Clopidogrel will work or not for their patients, hence they can make more informed decisions from the outset, selecting the most appropriate medication tailored to each patient’s genetic predisposition.

  You can see which stroke prevention medications are included in the Mantara PGx Test here.

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