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11/13/24, 7\:43 PM Guide | Prescribing antiplatelet therapy

Prescribing antiplatelet therapy

Table of contents

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 e

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 a
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 e
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.
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Dual antiplatelet therapy (DAPT)
Dual antiplatelet therapy (DAPT) involves aspirin and a second antiplatelet drug. The second antiplatelet drug is usually
continued for a set period of time (up to 12 months).
DAPT is used in acute coronary syndrome and patients who have coronary stents inserted. 5,6
This is typically aspirin in
combination with clopidogrel or ticagrelor, or aspirin paired with prasugrel if undergoing cardiac stent procedures.
1,5

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
reduce the e
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 e

The most common side e
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 e
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\:
Prasugrel\: seven days
Ticagrelor\: at least three days
Aspirin\: seven days
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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.

References

1. Joint Formulary Committee. B N F 8 6 . 2023
2. Hodson K and Whittlesea C. C l i n i c a l P h a r m a c y a n d T h e r a p e u t i c s . 6 th
edition 2018
th
3. Ritter JM, Flower RJ, Henderson G, Loke YK, MacEwan D, Robinson E, Fullerton J. R a n g a n d D a l e’ s P h a r m a c o l o g y . 10 edition
2023
4. 6. 8. 9. SanoLINK]
5. NICE. A c u t e C o r o n a r y S y n d r o m e . November 2020. Available from\: [LINK]
NICE. S t r o k e a n d t r a n s i e n t i s c h a e m i c a t t a c k i n o v e r 1 6 s \: d i a g n o s i s a n d i n i t i a l m a n a ge m e n t . April 2022. Available from\: [LINK]
7. Specialist Pharmacy Service. U s i n g c l o p i d o g r e l w i t h p r o t o n p u m p i n h i b i t o r s ( P P I s ) . September 2023. Available from\: [LINK]
MHRA. C l o p i d o g r e l a n d p r o t o n p u m p i n h i b i t o r s \: i n t e r a c t i o n – u p d a t e d a d v i c e . December 2014. Available from\: [LINK]
UKCPA. H a n d b o o k o f p e r i o p e r a t i v e m e d i c i n e s . 2024. Available from\: [LINK]
Source\: geekymedics.com
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