Antiplatelet Therapy For Stroke Prevention

  • Saira Loane Master's of Toxicology, Institute of Biomedical Research, University of Birmingham
  • Amy Mak MPharm in Pharmacy, Aston Universtiy

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Introduction

Stroke is a severe medical condition that occurs when the blood supply to the brain is cut off or blocked, which can happen due to a blood clot or ruptured blood vessels. Strokes are a medical emergency and need urgent care. The sooner a person receives stroke treatment, the less damage is likely to occur.1

Stroke can affect a person differently, depending on what part of the brain has restricted blood supply; this can affect your speech and how you think or move your body.2 

The main symptoms of stroke can be remembered with the word FAST

Face: The face may have dropped on one side, and the person may be unable to close their eyes or mouth.

Arm: The person suspected of a stroke may not be able to lift or hold their arms; this is because of numbness or weakness in one of the arms. 

Speech: Their speech may be slurred or garbled, or may not be able to talk at all despite appearing awake. They may also need help understanding what you are saying to them. 

Time: It's time to call 999 if you experience or see any of these symptoms..1

Types and causes of stroke 

Ischaemic stroke occurs when a clot blocks an artery supplying blood to your brain.

Haemorrhage strokes happen when the blood vessels rupture, causing a bleed in the brain; this means less blood gets to the brain cells, leading to cell death.

Mini-strokes or Transient Ischemic Attacks (TIA) happen when there is a disruption in the blood supply for a short time, causing symptoms such as temporary speech loss. TIA usually resolve after a few seconds, minutes.2 

Certain conditions can increase the risk of having a stroke, including:

  • High Blood pressure 
  • High Cholesterol 
  • Irregular heartbeats
  • Diabetes 

Significance of stroke prevention

You can significantly reduce the risks of having a stroke if you:

  • Eat well 
  • Take regular exercise 
  • Limit alcohol intake 
  • Avoid smoking 

If you have pre-existing health issues that can increase the chances of having a stroke, it's important to manage it effectively. For example, if you are on high blood pressure medication, taking it regularly can reduce the risk of developing a stroke. It's important to take medicines particularly if you had a stroke or TIA in the past, because the risks of having another stroke can greatly increase.1 

Understanding antiplatelet therapy

Platelets are small, colourless cells that are essential in forming blood clots. They are not actual cells and do not carry nuclei or nuclear DNA. In stroke, platelets play a role in ischemic or reperfusion injury.3

Platelets are one component of the blood vascular axis responsible for stopping bleeding. Activated platelets initiate hemostatic plug formation and provide scaffolding for coagulation activities.4

Platelet aggregation is the process by which platelets clump together at the injury site to form a clot. The process of platelet aggregation is complex and involves several steps, including adhesion, activation and aggregation. When a clot in an artery stops supplying blood to the brain, it causes a stroke. Clots can be formed when platelets clump together leading to blockage of the blood vessels, resulting in acute cardiovascular events such as stroke.5 

Activation and aggregation is an integral part of forming a blood clot. Antiplatelet drugs block the formation of blood clots. They work by inhibiting platelets from sticking together. It is suggested that this is how they exert their cardiovascular protective effects. There are four types of antiplatelet drugs available:

  1. Glycoprotein platelets inhibitors: block receptors on platelets that are involved in clotting.
  2. Platelets aggregation inhibitors: make platelets less sticky by interfering with their signalling molecules.
  3. Protease-activated receptor-1 antagonists: block receptors that activate platelets in response to clot formation. 
  4. Adenosine reuptake inhibitors: block enzymes involved in clotting.5

Comparative analysis of different antiplatelet agents

Current antiplatelet therapy substantially improves clinical outcomes in patients with coronary heart disease but at the cost of increased risk of bleeding. Aspirin, a powerful antiplatelet, is associated with a dramatic reduction in the risk of a first myocardial infarction, yet has little or no effect in the primary prevention of stroke.

It is only that taking Aspirin has shown a significant benefit in secondary prevention trials. There are two possible reasons why Aspirin works for secondary prevention of stroke but not for primary prevention. First, those at most risk of developing blood clots are identified, thereby maximising the benefit-to-risk ratio. Secondly, there is evidence that myocardial infarction and stroke cause platelet activation.3 

Benefits and risks of antiplatelet therapy in stroke prevention

According to the American Heart Association, antiplatelet drugs such as Aspirin or Aspirin with Dipyridamole and Clopidogrel alone are currently recommended for secondary prevention of stroke. These drugs can reduce recurrent ischemic events by 20% compared with placebo or no therapy. However, despite treatment, the risk of bleeding is substantial. Bleeding complications may offset the benefits of antiplatelet drugs in patients at increased risks of bleeding and low risks of recurrent ischemic events.7

In a randomised trial carried out in 2021, the risks of major bleeding and the dangers of recurrent ischemic stroke increase in parallel across bleeding risk groups in long-term secondary prevention after a TIA or minor stroke. 

The benefits of aspirin monotherapy outweigh the risks, irrespective of baseline bleeding risks. A recent study has drawn attention to the substantial risks associated with the long-term use of aspirin in the elderly population. The incidence of bleeding increases significantly with age, reaching an annualised rate of 4% in patients over 85 years old. 

The benefits of adding one extra antiplatelet have been investigated, and some trials observed a slight reduction in ischemic events during the use of aspirin and clopidogrel, but at the cost of significantly higher bleeding risk.7

Limitations and challenges in antiplatelet therapy usage

Aspirin and Clopidogrel present the cornerstone of treatment for secondary prevention of ischemic events in patients. 

A considerable number of patients continue to experience recurrent events of bleeding despite the use of these antiplatelet drugs. These observations have led to the development of antiplatelet drug resistance. The events of bleeding could not be attributed to drug resistance if the efficacy of antiplatelet agents was not tested in the affected patients. 

For Aspirin, the resistance involves inadequate or lack of inhibition of the enzyme, which interferes with signalling molecules whereas Clopidogrel resistance involves receptors signalling. 

Although current approved antiplatelet drugs have proven to improve patient outcomes, diabetic patients continue to have higher risks of adverse cardiovascular events compared with non-diabetic patients. Novel and more potent antiplatelet drugs currently under clinical development will be more useful in reaching these therapeutic goals.8

FAQ’s

How do I take antiplatelets?

Always take your medicine as prescribed by the healthcare provider. Take your medication at the same time every day. This will help you to take your medicine regularly and keep a steady level of medicines in your body.

What are the risks associated with antiplatelets? 

If you are taking antiplatelet drugs, you may experience a risk of bleeding in your brain or gastrointestinal tract. The risk of getting an infection can also increase. If you skip your dose or do not take them regularly, it may increases the risk of getting a heart attack, stroke and Mini-strokes or transient ischemic Attacks (TIAs).6

What safety measures do I need to follow?

  • Keep your healthcare provider informed about your antiplatelet drugs. Always keep a list of medications you are taking and their dosage.
  • Wear a medical bracelet or necklace that says you are taking this medicine. 
  • Avoid any activities that can lead to bruising or bleeding. 
  • You may need a regular blood test so that healthcare providers know how much medicine you need to take.
  • Avoid drinking alcohol and smoking completely.

When should I seek medical advice?

  • Nose bleed that lasts longer than 10 minutes 
  • Coughing or vomiting blood 
  • Feeling dizzy and cannot keep your balance 
  • Feeling confused and having trouble speaking 
  • Chest pain or difficulty in breathing.6

Summary

Enhanced antiplatelet therapy might be more effective than surgery in preventing stroke. Other stroke risk factors, such as antiplatelet mechanisms, may have a role in the preventative action of blood pressure and other stroke treatments. 

Unfortunately, all antiplatelets carry a potential risk of bleeding. The mechanisms by which this may happen have not been fully understood. As in other areas of stroke treatment, it is the balance between stroke efficacy in the reduction of symptomatic thrombotic events and the risk of bleeding that will define benefit. 
Drugs like beta-blockers and calcium channel blockers are included in the group in preventing stroke.

References

  • nhs.uk [Internet]. 2017 [cited 2024 Jan 8]. Stroke. Available from: https://www.nhs.uk/conditions/stroke/
  • British Heart Foundation [Internet]. [cited 2024 Jan 8]. Stroke - causes, signs and symptoms. Available from: https://www.bhf.org.uk/informationsupport/conditions/stroke
  • Smith NM, Pathansali R, Bath PM. Platelets and stroke. Vasc Med [Internet]. 1999 Aug [cited 2024 Jan 8];4(3):165–72. Available from: http://journals.sagepub.com/doi/10.1177/1358836X9900400307
  • Del Zoppo GJ. The role of platelets in ischemic stroke. Neurology [Internet]. 1998 Sep [cited 2024 Jan 9];51(3_suppl_3). Available from: https://www.neurology.org/doi/10.1212/WNL.51.3_Suppl_3.S9
  • NICE [Internet]. [cited 2024 Jan 9]. CKS is only available in the UK. Available from: https://www.nice.org.uk/cks-uk-only
  • Drugs.com [Internet]. [cited 2024 Jan 9]. Safe use of antiplatelet medication - what you need to know. Available from: https://www.drugs.com/cg/safe-use-of-antiplatelet-medication.html
  • Hilkens NA, Algra A, Diener HC, Bath PM, Csiba L, Hacke W, et al. Balancing benefits and risks of long-term antiplatelet therapy in noncardioembolic transient ischemic attack or stroke. Stroke [Internet]. 2021 Oct [cited 2024 Jan 9];52(10):3258–65. Available from: https://www.ahajournals.org/doi/10.1161/STROKEAHA.120.031755
  • Angiolillo DJ. Antiplatelet therapy in diabetes: efficacy and limitations of current treatment strategies and future directions. Diabetes Care [Internet]. 2009 Apr 1 [cited 2024 Jan 10];32(4):531–40. Available from: https://diabetesjournals.org/care/article/32/4/531/28922/Antiplatelet-Therapy-in-Diabetes-Efficacy-and

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This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Saira Loane

Master's of Toxicology, Institute of Biomedical Research, University of Birmingham

Saira Loane is an aspiring medical writer with several years of experience working in scientific
research and developing high-quality medical content.

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