Prescribing Antiplatelet Therapy

Introduction

Antiplatelets are a group of medications which reduce platelet formation and inhibit thrombus formation in the arterial circulation.¹

In this article, we will focus on the main antiplatelet agents in use: aspirin, clopidogrel, ticagrelor, prasugrel, and dipyridamole. We will discuss their roles, side effects, monitoring, and key points for safe prescribing in practice.

Mechanism of action

Aspirin

As well as being used for analgesia, aspirin is widely used as an antiplatelet.

Low dose aspirin at a dose of 75mg once daily inhibits the enzyme cyclooxygenase, which prevents prostaglandin mediated production of TXA2 (thromboxane A2) platelet aggregation for the life of the platelet. With regular oral administration of aspirin, TXA2 synthesis does not fully recover until affected platelets are replaced in seven to ten days.^2,3

Aspirin at a 300mg dose achieves rapid and substantial inhibition of platelet thromboxane synthesis.^2,3

Clopidogrel, ticagrelor and prasugrel

Clopidogrel, prasugrel and ticagrelor are all adenosine-diphosphate (ADP) receptor antagonists.

Clopidogrel and prasugrel inhibit ADP (adenosine diphosphate) induced platelet aggregation through irreversible inhibition of P2Y12 receptors on platelets for their lifespan. Ticagrelor inhibits the same receptor reversibly but is non-competitive.^2,3

Clopidogrel is a prodrug, which is metabolised by CYP450 enzymes, including CYP3A4 & CYP2C19, to an active metabolite which then exerts its effects on platelet aggregation.⁴

Dipyridamole

Dipyridamole inhibits platelet aggregation by inhibiting TXA2 synthesis, inhibiting phosphodiesterase and blocking the uptake of adenosine into red cells.3

Indications

Antiplatelets have a wide range of indications. They are commonly used for secondary prevention of cardiovascular disease in patients who have had a myocardial infarction or stroke/TIA, typically aspirin or clopidogrel lifelong.^5,6 

They are also used in the acute management of acute coronary syndrome, starting with an initial high loading dose of aspirin 300mg and a second antiplatelet (e.g ticagrelor, clopidogrel) before stepping down to maintenance dosing.^1,5

Aspirin is indicated for acute management of stroke, with 300mg given once daily for up to two weeks before stepping down to clopidogrel for secondary prevention.^1,6

Clopidogrel is the agent of choice for patients with symptomatic peripheral arterial disease requiring secondary prevention.¹

Dipyridamole is an older antiplatelet, however can be used with aspirin in combination following a stroke or TIA if intolerant to clopidogrel.⁶

Key interactions

Omeprazole and esomeprazole are proton pump inhibitors (PPIs) which are inhibitors of CYP2C19. As clopidogrel is activated by this enzyme, concomitant use can reduce the plasma levels of active clopidogrel. Therefore, when considering PPI therapy for patients on clopidogrel an alternative option should be considered such as lansoprazole.⁷

Other inhibitors of CYP2C19 include fluoxetine and fluconazole, and concomitant use is discouraged due to the potential to also reduce the efficacy of clopidogrel.⁸

Due to the increased risk of bleeding with antiplatelets, prescribing alongside any medication that can increase this risk further should be carefully considered, including NSAIDs, anticoagulants and SSRIs. Further detailed advice on the combinations can be found in the BNF.¹

Monitoring

Although no mandatory monitoring is indicated, it is advisable to review platelet count and bleeding risk periodically for any abnormalities, and in those with impaired renal function review the clinical need due to increased bleeding risk in renal impairment.¹

For ticagrelor, it is advised to monitor renal function one month after initiation in patients being treated for ACS.¹

Key side effects

The most common side effects from antiplatelets are gastrointestinal upset, including dyspepsia and ulceration, which can be more pronounced when using more than one in combination.

This can also result in gastrointestinal haemorrhage, particularly if the patient has additional risk factors. The risk can be reduced by prescribing gastroprotection with a proton pump inhibitor (PPI) such as omeprazole or lansoprazole.¹

Aspirin needs to be used with caution in those with pre-existing airway obstruction as it can cause bronchospasm and provoke an acute asthma attack.¹

Prasugrel can cause skin reactions, most commonly a rash, and ticagrelor is associated with dizziness, dyspnoea or gout in patients.¹

Due to dipyridamole’s effects on vasodilation, it can result in hot flushes, hypotension and tachycardia.¹

Antiplatelets and surgery

For patients on antiplatelets requiring surgery, the indication for the antiplatelet and the bleeding risk of the procedure need to be considered, as well as the method of anaesthesia.⁹

Suggested timeframes for withholding antiplatelets prior to surgery are:⁹

• Clopidogrel: five to seven days
• Prasugrel: seven days
• Ticagrelor: at least three days
• Aspirin: seven days

For patients where it is not possible to delay surgery in the timeframes suggested, it is advised to avoid spinal/epidural anaesthesia.⁹

If the patient had had a stent insertion within the previous month, consider delaying surgery until one month after insertion.⁹

The UKCPA Handbook of Perioperative Medicines website provides more information on antiplatelets and other medications related to surgery.

Editor

Dr Chris Jefferies

References

1. Joint Formulary Committee. BNF 86. 2023
2. Hodson K and Whittlesea C. Clinical Pharmacy and Therapeutics. 6^th edition 2018
3. Ritter JM, Flower RJ, Henderson G, Loke YK, MacEwan D, Robinson E, Fullerton J. Rang and Dale’s Pharmacology. 10^th edition 2023
4. Sanofi. Summary of Product Characteristics, Plavix. January 2024. Available from: [LINK]
5. NICE. Acute Coronary Syndrome. November 2020. Available from: [LINK]
6. NICE. Stroke and transient ischaemic attack in over 16s: diagnosis and initial management. April 2022. Available from: [LINK]
7. Specialist Pharmacy Service. Using clopidogrel with proton pump inhibitors (PPIs). September 2023. Available from: [LINK]
8. MHRA. Clopidogrel and proton pump inhibitors: interaction – updated advice. December 2014. Available from: [LINK]
9. UKCPA. Handbook of perioperative medicines. 2024. Available from: [LINK]